Cyanide Poisoning Summary

Common Causes

  • House fires (most common)
  • Industrial exposures
  • Cyanogenic foods
  • Medical treatments
  • Suicide/homicide attempts

Pathophysiology

  • Binds cytochrome oxidase
  • Blocks oxidative phosphorylation
  • Causes histotoxic hypoxia
  • Leads to lactic acidosis

Clinical Features

  • Early: Headache, nausea, anxiety
  • Moderate: Seizures, hypotension
  • Severe: Coma, cardiovascular collapse
  • Cherry red skin (classic but rare)

Diagnostic Clues

  • Lactate >7 mmol/L
  • Severe metabolic acidosis
  • High anion gap
  • Reduced venous-arterial PO2 gradient

Antidote Options

  • 1st line: Hydroxocobalamin
  • 2nd line: Cyanide Antidote Kit
  • 3rd line: 4-DMAP or Dicobalt edetate
  • Always: Sodium thiosulfate

Emergency Management

  • High-flow oxygen
  • No mouth-to-mouth resuscitation
  • Early antidote administration
  • Supportive care

Key Investigations

  • Lactate level
  • Arterial blood gas
  • Carboxyhemoglobin
  • Methemoglobin
  • Cyanide levels (delayed)

Cyanide Poisoning

Rapidly lethal toxidrome requiring immediate recognition and antidotal therapy

Introduction

Cyanide poisoning is a medical emergency that requires rapid diagnosis and treatment. It causes histotoxic hypoxia by inhibiting cellular respiration, leading to severe metabolic acidosis and potentially fatal outcomes if not treated promptly.

Time Critical: Untreated cyanide poisoning is rapidly lethal. Antidotal therapy must be given immediately when clinically suspected.

Causes and Exposure Sources

Fire-Related (Most Common)

  • Domestic fires in industrialized countries
  • Combustion of products containing carbon and nitrogen:
    • Wool, silk
    • Polyurethane (insulation/upholstery)
    • Polyacrylonitriles (plastics)
    • Melamine resins (household goods)
    • Synthetic rubber

Industrial Exposures

  • Metal extraction in mining
  • Electroplating in jewelry production
  • Photography
  • Plastics and rubber manufacturing
  • Hair removal from hides
  • Rodent pesticides and fumigants

Medical Sources

  • Laetrile/amygdalin (alternative cancer treatment)
  • Sodium nitroprusside (antihypertensive medication)

Dietary Sources

  • Rosaceae family plants:
    • Bitter almond, cherry laurel
    • Apricot, plum, peach, pear, apple
    • Contain cyanogenic glycosides in pits and seeds
  • Cassava root
  • Bamboo shoots
  • Soy

Other Sources

  • Ingestion of cyanide salts (KCN, NaCN)
  • Suicide and homicidal/terrorist acts
  • Illicit synthesis of phencyclidine
  • Ingestion of acetonitrile (artificial nail polish remover)
  • Cigarette smoking

Pathophysiology

Cyanide causes histotoxic hypoxia by binding to mitochondrial cytochrome oxidase, preventing cellular oxygen utilization despite adequate oxygen delivery.

Mechanism of Action

  • Binds to and inhibits mitochondrial cytochrome oxidase
  • Prevents oxidative phosphorylation and aerobic respiration
  • Forces cells to switch to anaerobic metabolism
  • Results in functional "histotoxic" hypoxia

Metabolic Consequences

  • Anaerobic respiration produces lactic acid
  • Development of severe metabolic acidosis
  • Hydrogen ions accumulate (not consumed in ATP production)
  • Serum bicarbonate decreases as it buffers excess acid
  • Increased anion gap metabolic acidosis

Target Organs

Cardiovascular and Central Nervous Systems are particularly vulnerable to cyanide toxicity due to their high oxygen demands. The basal ganglia show particular sensitivity, which can lead to delayed-onset Parkinsonism in survivors.

Clinical Features

Early Features (Minutes)

  • Headache
  • Nausea, dizziness
  • Anxiety, restlessness
  • Metallic taste
  • Tachycardia, palpitations
  • Hypertension
  • Tachypnea

Moderate Toxicity

  • Brief episodes of loss of consciousness
  • Seizures
  • Vomiting
  • Bradycardia
  • Hypotension
  • Smell of bitter almonds on breath
  • Flushed skin with 'cherry red' color (classic but rare)

Severe Poisoning

  • Deep coma
  • Fixed, unreactive pupils
  • Cardiovascular collapse
  • Respiratory depression
  • Myocardial ischemia
  • Cardiac arrhythmias
  • Pulmonary edema
  • Cyanosis (late sign, may be absent)

Time Course and Special Considerations

Exposure Route Onset of Symptoms Special Features
Inhalational Seconds Rapid onset, most dangerous route
Ingestion Minutes to hours Gastric irritation, vomiting, abdominal pain
Dermal Minutes to hours Delayed onset, depends on exposure extent

Neurological Sequelae: Survivors of severe cyanide poisoning may develop delayed-onset Parkinsonism or other neurologic sequelae due to basal ganglia sensitivity.

Diagnosis

Cyanide poisoning is uncommon and requires a high index of suspicion. Consider in patients with altered mental status and unexplained metabolic acidosis.

Clinical Suspicion

Diagnostic Indicators

Laboratory Findings

  • Lactate levels:
    • >7 mmol/L suggests cyanide poisoning
    • < 10 mmol/L = mild poisoning
    • 10-15 mmol/L = moderate poisoning
    • >15 mmol/L = severe poisoning
  • Severe metabolic acidosis with increased anion gap
  • Reduced venous-arterial PO2 gradient

Additional Testing

  • Carboxyhemoglobin and methemoglobin levels (co-oximetry)
  • Particularly important in fire victims (CO exposure)
  • Drug exposures causing methemoglobinemia
  • Blood cyanide concentrations (rarely available acutely)

Note: Blood cyanide concentrations may not correlate with toxicity and results are rarely available in time to guide acute management. Clinical diagnosis is essential.

Emergency Management

Immediate Action Required: If clinical history and examination suggest cyanide poisoning, administer antidotal therapy immediately unless contraindicated.

General Treatment

Initial Resuscitation
  1. Secure airway, breathing, and circulation
    • Intubation is usually required
    • Administer high-flow oxygen by non-rebreather face mask
    • Do NOT perform mouth-to-mouth resuscitation
  2. Decontamination for dermal exposure with proper precautions
  3. Activated charcoal (50g adults, 1g/kg children, max 50g) if airway protected
  4. Treat hypotension with IV fluid boluses and vasopressors
  5. Treat seizures with benzodiazepines
  6. Consult medical toxicologist or poison control center

Antidotal Treatment Protocol

First Line: Hydroxocobalamin Available

  • Hydroxocobalamin: 70 mg/kg up to 5 g IV (standard adult dose 5 g)
  • PLUS Sodium thiosulfate (25%): 1.65 mL/kg up to 50 mL IV
  • May repeat sodium thiosulfate once (max dose 12.5 g)

Second Line: Cyanide Antidote Kit

  • Amyl nitrite: Inhaled for 30 seconds/minute for 3 minutes
  • Sodium nitrite (3%): 10 mg/kg up to 300 mg slow IV
  • Sodium thiosulfate (25%): 1.65 mL/kg up to 50 mL IV
  • May repeat both nitrite and thiosulfate once

Uncertain Diagnosis or Nitrite Contraindications

  • Sodium thiosulfate (25%): 1.65 mL/kg up to 50 mL IV
  • May repeat once
  • Use when cyanide toxicity possible but not certain
  • Use when contraindications to nitrites exist

Alternative Antidotes (Limited Availability)

  • 4-DMAP (5%): 5 mL IV over one minute OR
  • Dicobalt edetate (1.5%): 20 mL IV over one minute
  • Use only if other antidotes unavailable and cyanide toxicity confirmed

Important: Nitrites are contraindicated in patients with significant carbon monoxide exposure as they may worsen tissue hypoxia. Hydroxocobalamin is preferred in smoke inhalation victims.

Special Considerations

Fire Victims

  • Most common scenario for cyanide poisoning
  • Often combined with carbon monoxide poisoning
  • Hydroxocobalamin preferred over nitrites
  • Check carboxyhemoglobin levels
  • Consider hyperbaric oxygen for significant CO exposure

Pediatric Considerations

  • Weight-based dosing for all antidotes
  • Higher risk of methemoglobinemia with nitrites
  • Hydroxocobalamin preferred in children
  • Careful fluid management in hypotension

Pregnancy

  • Treat the mother aggressively - fetal survival depends on maternal survival
  • Hydroxocobalamin is preferred in pregnancy
  • Nitrites may cause fetal methemoglobinemia
  • Consult obstetrics for fetal monitoring