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Injury and poisoning

Cyanide poisoning

Cyanide poisoning is a life-threatening toxic exposure that blocks cellular oxygen use at the mitochondrial level, most often from smoke inhalation in structure fires, industrial accidents, or suicide attempts. It affects fire victims, industrial workers, and occasionally patients on prolonged high-dose nitroprusside infusions. The single most testable fact: cyanide inhibits cytochrome c oxidase (complex IV), causing a severe lactic acidosis despite normal oxygen saturation and a narrow arteriovenous oxygen difference.

Practice questionsHigh-yield facts
ICD-10T65.0
Typical patientSmoke inhalation victim or industrial chemical worker
Key findingSevere lactic acidosis with normal SpO2
First-line treatmentHydroxocobalamin, supportive oxygen, decontamination
6 min readFor medical studentsUpdated 2026-10-14

Definition and epidemiology

Cyanide poisoning results from exposure to hydrogen cyanide gas, cyanide salts, or cyanide-releasing compounds that halt aerobic cellular respiration. It is a classic cause of rapid, lethal chemical asphyxiation despite adequate oxygen delivery to tissues.

  • Most common real-world cause: smoke inhalation from house or industrial fires (burning plastics, wool, synthetic foams release hydrogen cyanide)
  • Occupational exposure: electroplating, metal extraction (gold/silver mining), fumigation, photography, and chemical synthesis industries
  • Iatrogenic cause: prolonged or high-dose sodium nitroprusside infusion, especially with hepatic impairment (which limits detoxification to thiocyanate)
  • Other sources: ingestion of amygdalin-containing seeds (apricot, apple, cherry pits) in large quantities, and laetrile (alternative medicine product)
  • Deliberate exposure: suicide attempts and historically, chemical warfare and judicial execution
  • Exact incidence is hard to establish because many cases occur as a component of smoke inhalation and are underreported as isolated cyanide toxicity
High-yield for exams
  • Cyanide inhibits cytochrome c oxidase (complex IV), blocking oxidative phosphorylation despite adequate oxygen delivery
  • Classic lab clue: severe lactic acidosis with a narrow arteriovenous oxygen difference and normal pulse oximetry
  • Most common real-world cause is smoke inhalation from structure fires, not isolated industrial exposure
  • Hydroxocobalamin is the preferred first-line antidote, especially when carbon monoxide co-exposure is possible
  • Sodium thiosulfate provides a sulfur donor for rhodanese to convert cyanide to renally excreted thiocyanate
  • Nitroprusside infusions can cause cyanide toxicity, particularly with high doses or hepatic impairment (whereas renal impairment leads to thiocyanate toxicity)
  • Bitter almond breath odor and cherry-red skin are classic but unreliable/inconsistent exam findings
  • Do not delay antidote treatment waiting for a confirmatory whole blood cyanide level

Etiology and risk factors

Common sources

  • Combustion of nitrogen-containing synthetic materials (house fires, especially upholstery, carpets, and insulation)
  • Industrial cyanide salts: sodium cyanide, potassium cyanide
  • Nitroprusside metabolism (releases cyanide ions as a byproduct)
  • Cyanogenic glycosides in certain plants and seeds
  • Acetonitrile-containing products (nail glue remover) in pediatric exposures

Risk factors for severity

  • Enclosed-space fire exposure (higher concentration, concurrent carbon monoxide co-exposure)
  • Prolonged nitroprusside infusion, particularly with hepatic dysfunction (impaired rhodanese-mediated detoxification to thiocyanate); note that renal impairment instead predisposes to thiocyanate toxicity, since thiocyanate is cleared by the kidneys
  • Occupational exposure without adequate protective equipment
  • Co-ingestion or combined toxic exposures that delay recognition

Pathophysiology

Cyanide ion binds the ferric (Fe3+) heme iron of cytochrome c oxidase (complex IV) in the mitochondrial electron transport chain. This blocks the final step of oxidative phosphorylation, halting ATP production despite normal oxygen delivery to tissues.

  • Cells shift to anaerobic glycolysis, producing lactic acid and causing severe metabolic (lactic) acidosis
  • Oxygen cannot be extracted or utilized by tissues, so venous blood remains oxygen-rich, narrowing the arteriovenous oxygen difference and sometimes giving venous blood an abnormally bright red color
  • Tissues most dependent on aerobic metabolism (brain, heart) are affected earliest and most severely
  • Endogenous detoxification: cyanide is normally converted by the enzyme rhodanese to thiocyanate (using thiosulfate as a sulfur donor), then renally excreted; this pathway is overwhelmed in significant poisoning
  • Co-exposure to carbon monoxide in fire victims compounds tissue hypoxia through a separate mechanism (impaired oxygen carriage by hemoglobin)

Clinical features

Onset is rapid, often within seconds to minutes for inhaled hydrogen cyanide, and may be delayed with ingestion of salts or glycosides.

Early/mild

  • Headache, dizziness, anxiety, confusion
  • Nausea, vomiting
  • Tachypnea, tachycardia, flushing

Severe

  • Seizures, coma
  • Bradycardia progressing to cardiovascular collapse
  • Severe metabolic acidosis with compensatory hyperventilation
  • Classic but inconsistent findings: bitter almond odor on breath (only detectable by a subset of people genetically), cherry-red skin discoloration (uncommon in practice)
  • Normal or near-normal pulse oximetry despite clinical hypoxia-like state (oxygen is present but unusable)
  • In fire victims: soot in airway, singed nasal hairs, and signs of concurrent carbon monoxide toxicity (which can also cause cherry-red skin)

Diagnosis

Diagnosis is primarily clinical and based on exposure history plus characteristic laboratory clues, because cyanide blood levels are not available rapidly enough to guide emergency treatment.

Supportive clues

  • History of smoke inhalation, industrial exposure, or suspected ingestion
  • Severe anion-gap metabolic (lactic) acidosis out of proportion to apparent hypoxia
  • Elevated serum lactate (lactate greater than 10 mmol/L in a fire victim is highly suggestive)
  • Narrow arteriovenous oxygen difference on co-oximetry/blood gas sampling
  • Normal or elevated central venous oxygen saturation despite clinical shock

Confirmatory testing

  • Whole blood cyanide concentration can confirm diagnosis retrospectively but turnaround is too slow for acute management decisions
  • Co-oximetry to assess concurrent carboxyhemoglobin (carbon monoxide) in fire-related cases
  • ECG and continuous cardiac monitoring for dysrhythmias

Treatment should never be delayed pending laboratory confirmation when clinical suspicion is high.

Differential diagnosis

  • Carbon monoxide poisoning (frequently coexists in fire victims; distinguished by carboxyhemoglobin level, though both cause bright red skin changes)
  • Methemoglobinemia (cyanosis unresponsive to oxygen, chocolate-brown blood, different co-oximetry pattern)
  • Hydrogen sulfide poisoning (rotten egg odor, also blocks cytochrome c oxidase, seen in sewage/industrial exposure)
  • Severe sepsis or septic shock (lactic acidosis, but typically with a different clinical trajectory and infectious source)
  • Salicylate or other toxic ingestion causing anion-gap metabolic acidosis
  • Status epilepticus or primary cardiac arrest from other causes in undifferentiated collapse

Management

Management is a medical emergency requiring immediate supportive care and antidotal therapy; treatment decisions should be based on clinical suspicion, not waiting for confirmatory cyanide levels.

Immediate steps

  • Remove from the source and ensure scene safety (rescuers need appropriate protection)
  • High-flow 100% supplemental oxygen regardless of pulse oximetry reading
  • Airway, breathing, circulation support; intubation and mechanical ventilation if needed
  • Decontaminate skin/clothing if dermal or particulate exposure occurred

Antidotes

  • Hydroxocobalamin is first-line in most current US and European guidelines: binds cyanide directly to form cyanocobalamin, which is renally excreted; favored because it is effective, has a favorable safety profile, and does not worsen oxygen-carrying capacity (useful when carbon monoxide co-exposure is possible)
  • Sodium thiosulfate may be given alongside hydroxocobalamin or as part of older antidote kits; provides sulfur substrate to accelerate rhodanese-mediated conversion of cyanide to thiocyanate
  • Older cyanide antidote kits also contained amyl nitrite and sodium nitrite (induce methemoglobinemia, which binds cyanide); these are used less often now because they reduce oxygen-carrying capacity, which is a particular concern with concurrent carbon monoxide poisoning common in fire victims
  • Guideline consensus favors hydroxocobalamin as the preferred first agent in smoke-inhalation-associated cyanide toxicity specifically because nitrite-induced methemoglobinemia is undesirable in that setting

Supportive care

  • Correct metabolic acidosis as needed with fluids; sodium bicarbonate may be used for severe acidemia per clinical judgment
  • Treat seizures with standard anticonvulsants
  • Hemodynamic support with vasopressors if shock persists
  • Monitor for concurrent carbon monoxide poisoning and treat accordingly (high-flow oxygen, consider hyperbaric oxygen per local protocol and severity)

Complications and prognosis

Prognosis depends heavily on the dose, duration of exposure, and speed of treatment initiation.

  • Rapid death from cardiovascular collapse and respiratory arrest can occur within minutes in high-dose exposures
  • Survivors of severe poisoning may have persistent neurologic injury (anoxic brain injury, parkinsonism-like movement disorders, cognitive deficits) due to the brain's high sensitivity to impaired oxidative metabolism
  • Myocardial injury and dysrhythmias may occur from direct cardiac toxicity
  • With prompt recognition and antidote administration, especially in isolated or mild-to-moderate exposures, full recovery is common
  • Fire-related cases carry a worse prognosis when combined with carbon monoxide poisoning, thermal airway injury, and hypoxia from the fire environment itself
Mnemonic

Cyanide Can't CO2 (cells Can't use O2): think 'complex IV blocked, lactate up, pulse ox normal'

Practice questions

1. A 34-year-old man is rescued from a burning apartment and brought to the emergency department. He is confused with a respiratory rate of 32/min. Pulse oximetry reads 98% on room air. Arterial blood gas shows severe metabolic acidosis with a lactate of 14 mmol/L. Which of the following best explains this patient's acid-base abnormality?

Answer: B. The combination of a normal pulse oximetry reading with severe lactic acidosis is the classic pattern of cyanide toxicity: oxygen is delivered normally but cannot be used because cytochrome c oxidase is blocked, forcing cells into anaerobic metabolism. Carbon monoxide would typically show reduced oxygen delivery and would not read as 98% on standard pulse oximetry (it can falsely elevate readings), but the key distinguishing clue here is the markedly elevated lactate with preserved oxygenation, pointing to a cellular utilization defect rather than a delivery or transport defect.

2. A 58-year-old woman with hypertensive emergency is treated with a prolonged high-dose sodium nitroprusside infusion. On day 3, she develops confusion, metabolic acidosis, and an elevated lactate. Which of the following is the most appropriate first-line antidote?

Answer: C. Prolonged nitroprusside infusion releases cyanide as a metabolic byproduct, and this patient's presentation with confusion, acidosis, and elevated lactate is consistent with cyanide toxicity. Hydroxocobalamin is the preferred first-line antidote because it directly binds cyanide to form renally excreted cyanocobalamin without inducing methemoglobinemia, unlike nitrite-based antidotes.

3. A 45-year-old firefighter is exposed to smoke during a warehouse fire and develops signs concerning for both carbon monoxide and cyanide toxicity. Why is hydroxocobalamin generally preferred over sodium nitrite in this specific clinical scenario?

Answer: C. Sodium nitrite treats cyanide toxicity by inducing methemoglobinemia, which binds cyanide but also reduces the blood's already-compromised oxygen-carrying capacity, a particular problem when carbon monoxide poisoning is also present. Hydroxocobalamin binds cyanide directly without this effect, making it the safer and preferred choice in combined smoke inhalation exposures.

Frequently asked questions

What causes cyanide poisoning?

Cyanide poisoning is most often caused by inhaling smoke from burning synthetic materials in house or industrial fires. Other causes include industrial exposure to cyanide salts, ingestion of cyanogenic plant seeds in large amounts, and prolonged high-dose sodium nitroprusside infusions in hospitalized patients. Deliberate ingestion for self-harm is also an important cause encountered in emergency settings.

What are the first symptoms of cyanide poisoning?

The earliest symptoms are usually headache, dizziness, confusion, anxiety, nausea, and rapid breathing and heart rate. These occur within seconds to minutes of significant inhalational exposure. As toxicity worsens, symptoms progress to seizures, loss of consciousness, and cardiovascular collapse, so early recognition and prompt removal from exposure are critical.

How is cyanide poisoning diagnosed?

Diagnosis is mainly clinical, based on exposure history (such as a structure fire) combined with severe lactic acidosis and an unexpectedly normal oxygen saturation. Blood cyanide levels can confirm the diagnosis but take too long to return for emergency decision-making. Clinicians treat based on strong clinical suspicion rather than waiting for lab confirmation.

Is cyanide poisoning curable?

Yes, cyanide poisoning is treatable and often fully reversible if recognized and treated promptly with antidotes like hydroxocobalamin and supportive care. Outcomes depend on the dose and duration of exposure before treatment begins. Severe, prolonged exposures can cause lasting brain or heart injury or death despite treatment.

Cyanide poisoning vs carbon monoxide poisoning — what is the difference?

Both impair cellular oxygen use and commonly occur together in fire victims, but by different mechanisms. Carbon monoxide binds hemoglobin, reducing oxygen-carrying capacity, while cyanide blocks cytochrome c oxidase so cells cannot use oxygen that is delivered. Carboxyhemoglobin levels confirm carbon monoxide exposure, while cyanide diagnosis relies more on clinical pattern since blood levels return too slowly.

Key drugs

hydroxocobalaminsodium thiosulfatesodium nitriteamyl nitritesodium bicarbonate
Carbon monoxide poisoningMethemoglobinemiaHydrogen sulfide poisoningSmoke inhalation injuryLactic acidosisSalicylate poisoningNitroprusside toxicitySeptic shock

Sources and further reading

StatPearls (NCBI Bookshelf)MedlinePlusWHO ICD-10: T65.0

Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.