Cyanide Poisoning: Diagnosis and Treatment

Cyanide Poisoning: Diagnosis and Causes

  • Most common cause in the United States: fires.

  • Firefighters and individuals involved in fires are at risk.

  • Cyanide exists in gas, liquid, or solid forms.

  • Routes of exposure: inhalation, ingestion, skin absorption.

  • Causes include:

    • Smoke inhalation (most common in the US).

    • Suicide attempts via ingestion.

    • Medications (e.g., sodium nitroprusside).

    • Industrial exposure.

    • Polyurethane (bubble wrap).

Mechanism of Action

  • Cyanide binds to ferric iron (Fe3+Fe^{3+}).

  • Target 1: Ferric in methemoglobin.

  • Target 2: Ferric in cytochrome C oxidase (mitochondria).

  • In the absence of methemoglobin, cyanide binds to cytochrome C oxidase.

  • Binding to cytochrome C oxidase:

    • Irreversible enzyme inhibition.

    • Inhibition of complex 4 (cytochrome a/a3) of the electron transport chain.

    • Oxygen cannot act as an electron acceptor.

    • Shift to anaerobic glycolysis for energy production.

    • Leads to lactic acidosis.

  • Binding to methemoglobin:

    • Forms cyanomethemoglobin.

    • Liver rhodanese, with sodium thiosulfate, converts it to thiocyanate.

    • Thiocyanate is excreted in the urine.

Pathophysiology

  • Inhibition of Complex 4 (cytochrome a/a3):

    • No ATP formation.

    • Mitochondria cannot utilize oxygen.

    • Shift to anaerobic glycolysis.

    • Results in lactic acid production and lactic acidosis.

    • Leads to high anion gap metabolic acidosis.

    • Normal anion gap: less than 12.

  • Impact on Oxygen Concentration Gradient:

    • Normally, tissues use oxygen, creating a concentration gradient between hemoglobin and tissue.

    • In cyanide poisoning, tissues cannot use oxygen.

    • No concentration gradient for oxygen to flow from hemoglobin to tissue.

    • Oxygen remains bound to hemoglobin.

    • Venous oxygen content becomes high, similar to arterial oxygen content.

    • Partial pressure of oxygen in the artery (PaO2) ≈ partial pressure of oxygen in the vein (PvO2).

Key Points and Considerations

  • Despite the abundance of oxygen, it cannot be utilized by the mitochondria.

  • Apricots and almonds contain amygdalin, which is hydrolyzed into hydrogen cyanide.

  • Large quantities of almonds can lead to cyanide poisoning.

  • Patient's breath may smell like bitter almonds.

Clinical Presentation Scenarios

  • Firefighter in a coma with almond-like breath after a fire.

  • Patient on sodium nitroprusside suddenly collapses with metabolic acidosis.

  • Factory worker comatose after an industrial explosion.

  • Pharmacist with major depressive disorder presents with confusion, seizure, and loss of consciousness.

Symptoms vs. Signs

  • Symptoms: what the patient complains of.

  • Signs: what the doctor observes.

  • Symptoms:

    • Weakness (due to lack of ATP).

    • Tissue hypoxia.

    • Epidermal pain.

    • Chest pain.

    • Neurological issues: headache, vertigo, dizziness, seizure, coma (similar to CO poisoning).

  • Signs:

    • Dilated pupils.

    • Diaphoresis (excessive sweating).

    • Arrhythmia.

    • Cardiovascular collapse.

    • Possible decrease in heart rate and blood pressure.

    • Increased respiratory rate and shortness of breath.

    • Cherry-red skin (due to high venous oxygen content).

Laboratory Findings

  • Arterial and Venous Blood Gases:

    • PaO2: Normal.

    • PvO2: Higher than normal.

    • PaO2 ≈ PvO2.

    • AV oxygen difference decreased (less than 10%).

  • Acid-Base Balance:

    • High anion gap metabolic acidosis (due to lactic acidosis).

    • pH: less than 7.35 (normal: 7.35-7.45).

    • Decreased bicarbonate.

    • Increased anion gap: more than 12.

  • Blood Labs:

    • Increased blood lactate level (greater than 10).

    • Increased plasma cyanide concentration.

    • EKG: nonspecific findings, sinus tachycardia most common.

    • Carboxyhemoglobin concentration: to rule out CO poisoning.

    • Methemoglobin level: to monitor therapy.

Normal Physiology vs. Cyanide Effects

  • Normal:

    • Air with oxygen (FiO2).

    • Oxygen to lungs (PaO2).

    • Oxygen to arterial blood (PaO2).

    • Oxygen binds to hemoglobin (SaO2).

    • Oxygen to tissue for electron transport chain; produces carbon dioxide.

    • Carbon dioxide to hemoglobin (carbaminohemoglobin).

    • Venous blood (PvO2) back to lungs, exhaling carbon dioxide.

  • Effect of Cyanide:

    • FiO2: Normal.

    • PaO2 (alveoli): Normal.

    • PaO2: Normal.

    • SaO2: Normal.

    • PvO2: High.

    • Arterial oxygen content: Normal.

    • Venous oxygen content: Increased.

  • Cellular Impact:

    • Mitochondria cannot utilize oxygen.

    • Oxygen is released from hemoglobin to tissue, but mitochondria can't use it.

    • Cyanide poisoning generally does not shift the oxygen binding curve.

Management of Cyanide Poisoning

  • Remove clothes; wash body with soap and water (cyanide can absorb through skin).

  • Treat if cyanide poisoning is suspected; do not wait for labs.

  • Administer 100% oxygen; consider hyperbaric oxygen.

  • ABCs: Airway, Breathing, Circulation.

  • Establish IV line and continuous EKG monitoring.

    Administer cyanide antidote.

    • Triad: hydroxocobalamin, sodium nitrite, sodium thiosulfate.

  • Sodium Thiosulfate:

    • Helps cyanomethemoglobin convert to thiocyanate, which is excreted in urine.

  • Sodium Nitrite:

    • Converts normal hemoglobin to methemoglobin.

    • Methemoglobin binds cyanide to form cyanomethemoglobin.

    • Sodium thiosulfate converts cyanomethemoglobin to thiocyanate, excreted in urine.

  • Hydroxocobalamin:

    • Combines directly with cyanide to form cyanocobalamin.

    • Cyanocobalamin is excreted in urine.

Detailed Antidote Mechanisms

  • Sodium Nitrite:

    • Hemoglobin (ferrous) Fe2+Fe^{2+} converted to methemoglobin (ferric) Fe3+Fe^{3+}.

    • Cyanide binds to ferric in methemoglobin, forming cyanomethemoglobin.

    • Sodium thiosulfate converts cyanomethemoglobin to thiocyanate.

    • Methylene blue can later convert methemoglobin back to hemoglobin.

  • Hydroxocobalamin (Vitamin B12):

    • Binds cyanide, forming cyanocobalamin and is excreted in urine.

  • Avoid Methylene Blue During Acute Treatment:

    • Methylene blue converts methemoglobin back to hemoglobin (counterproductive during acute phase).

    • Wait until cyanide is cleared before using methylene blue.

    • Monitor methemoglobin levels; avoid excessive methemoglobinemia.

Important Distinctions

  • Sodium nitroprusside leads to cyanide poisoning.

  • Sodium nitrite and sodium thiosulfate treat cyanide poisoning.

  • Sodium nitroprusside, cyanide, and sodium nitrite all can cause hypotension and result in death or reflex tachycardia.

Fundoscopy in Cyanide Poisoning

  • Difficult to distinguish between retinal arteries and veins during fundoscopy.

  • Arterial and venous partial pressures of oxygen are similar, giving both vessels a bright red color.