DESCRIPTION

The cyanide antidote package contains antidotes for cyanide and hydrogen sulfide toxicity.

FORMS AND USES

The cyanide antidote package (also known as cyanide kit) contains:

• 12 pearls of amyl nitrite for inhalation
• two ampules of sodium nitrite 300 mg in 10 cc of sterile water for injection
• two vials of sodium thiosulfate 12.5 g in 50 cc of sterile water for injection

MECHANISM OF ACTION

• Cyanide binds ferric iron (Fe³⁺) contained in cytochrome oxidase, thereby impairing adenosine triphosphate (ATP) production and resulting in anoxic tissue injury.
• Cyanide does not significantly bind to hemoglobin (ferrous iron, Fe²⁺).
• The cyanide antidote package works by producing methemoglobinemia.
  • Amyl nitrite is used as a temporizing measure until sodium nitrite can be infused.
  • Sodium nitrite oxidizes the ferrous iron in hemoglobin to ferric iron, producing methemoglobin.
  • Methemoglobin binds cyanide avidly and is thought to reverse cyanide toxicity by removing cyanide from cytochrome oxidase; the resulting complex of cyanide and methemoglobin is termed cyanmethemoglobin.
  • Cyanmethemoglobin may subsequently dissociate slowly to cyanide and methemoglobin, allowing cyanide toxicity to continue or recur.
  • Sodium thiosulfate is used to complete the elimination of cyanide; the enzyme rhodanese catalyzes the reaction of thiosulfate and cyanmethemoglobin to produce thiocyanate, a water-soluble product that is excreted in urine.
• Toxicity often develops more slowly with cyanide ingestion than with inhalation because absorption takes longer.

DRUG AND DISEASE INTERACTIONS

Use of the cyanide kit in a patient with preexisting methemoglobinemia may produce overwhelming methemoglobinemia.

PREGNANCY AND LACTATION

The effect in pregnancy is unknown, but the benefits are thought to outweigh the risks.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

CYANIDE POISONING

• Patients with known cyanide poisoning and with serious clinical effects (hypotension, hyperkalemia, metabolic acidosis, altered mental status) should receive the antidote.
• In the case of a patient with known cyanide exposure, but in whom clinical effects have not developed, treatment with the sodium thiosulfate component of the kit alone is recommended. This scenario would be most common after ingestion of a cyanide-containing product.
• In cases of suspected cyanide poisoning (e.g., altered mental status and metabolic acidosis in a smoke inhalation victim), treatment with the sodium thiosulfate component of the kit alone is recommended. In these cases, addition of methemoglobin (which would result from sodium nitrite injection) to carboxyhemoglobin may further decrease the oxygen-carrying capacity of hemoglobin.
• Cyanide toxicity associated with nitroprusside infusion.

HYDROGEN SULFIDE POISONING

Administration of the sodium nitrite component of the kit alone in conjunction with supportive therapy within 15 to 20 minutes of exposure is supported by anecdotal reports.

Section Outline:

• CYANIDE POISONING
• HYDROGEN SULFIDE POISONING

CONTRAINDICATIONS

• Sodium nitrite should not be used in clinical situations where the methemoglobin level is already 20% to 30%, in order to avoid compromise of oxygen delivery to tissues.
• If time allows, smoke inhalation victims should have their carboxyhemoglobin level measured when use of the sodium nitrite component is anticipated; the use of sodium thiosulfate alone should be considered because it will increase cyanide excretion without inducing methemoglobinemia.
• There are no known contraindications for the sodium thiosulfate component alone.

ADVERSE EFFECTS

• Hypotension induced by rapid infusion of sodium nitrite may be treated by reducing the infusion rate and administering crystalloid intravenous fluid and pressors.
• Cyanosis or hypoxia may occur if methemoglobinemia exceeds 30%.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

KNOWN CYANIDE POISONING WITH SERIOUS CLINICAL EFFECTS

Amyl Nitrite Ampules

Until vascular access is obtained, a crushed ampule is held to the nose or mouth, or in front of ventilation bag intake valve for 30 seconds of each minute.

Sodium Nitrite Injection

• This should be administered as soon as intravenous access has been established.
• Adult dose is 10 ml (300 mg of 3% solution) diluted to 100 ml with 0.9% sodium chloride and infused intravenously over 20 minutes; the infusion should be slow to prevent hypotension.
• Pediatric dose is 0.15 to 0.30 ml/kg of a 3% solution diluted to 100 ml with 0.9% sodium chloride and infused intravenously over 20 minutes; infusion should be slow to prevent hypotension.
• Methemoglobin level should be obtained 30 minutes after administration.
• If anemia complicates interpretation of the methemoglobin level, the hemoglobin concentration can be used to guide therapy.
  • If the hemoglobin level is 8 g, the initial dose of sodium nitrite should be 0.22 ml/kg (6.6 mg/kg), and the initial dose of sodium thiosulfate should be 1.1 ml/kg.
  • If the hemoglobin level is 10 g, the initial dose of sodium nitrite should be 0.27 ml/kg (8.3 mg/kg), and the initial dose of sodium thiosulfate should be 1.35 ml/kg
  • If the hemoglobin level is 12 g, the initial dose of sodium nitrite should be 0.33 ml/kg (10 mg/kg), and the initial dose of sodium thiosulfate should be 1.65 ml/kg
  • If the hemoglobin level is 14 g, the initial dose of sodium nitrite should be 0.39 ml/kg (11.6 mg/kg), and the initial dose of sodium thiosulfate should be 1.95 ml/kg

Sodium Thiosulfate

• Adult dose is sodium thiosulfate 50 ml (12.5 g of 25% solution) over several minutes.
• Pediatric dose is sodium thiosulfate 1.65 ml/kg up to 50 ml (25% solution) over several minutes.

If clinical evidence of cyanide poisoning persists for 30 minutes or recurs after an initial response to treatment, sodium nitrite and sodium thiosulfate doses may be repeated; some authorities suggest that half of the initial dose be used.

KNOWN CYANIDE EXPOSURE, BUT CLINICAL EFFECTS HAVE NOT DEVELOPED

Use of sodium thiosulfate alone should be considered in patients with cyanide ingestion.

SUSPECTED CYANIDE POISONING

Many practitioners use sodium thiosulfate injection alone in cases in which the oxygen-carrying capacity of blood is impaired, for example, in a victim of smoke inhalation (carbon monoxide poisoning).

CYANIDE TOXICITY ASSOCIATED WITH NITROPRUSSIDE INFUSION

• Prevention of cyanide toxicity.
• Concomitant infusion of both nitroprusside and sodium thiosulfate has been used.
• Administer infusion containing 10 mg of thiosulfate for every 1 mg of nitroprusside (10 ml of 0.1% solution of nitroprusside and 50 ml of 1% sodium thiosulfate); the admixture is stable up to 8 days.
• If cyanide toxicity has already occurred, use the full cyanide package as directed for symptomatic cyanide poisoning.

HYDROGEN SULFIDE POISONING

• Sodium nitrite should be administered within 15 to 20 minutes of exposure.
  • Adult dose is 10 ml (300 mg of 3% solution) diluted to 100 ml with 0.9% NaCl intravenously over 20 minutes, infused slowly to prevent hypotension.
  • Pediatric dose is 0.15 to 0.30 ml/kg of a 3% solution diluted to 100 ml with 0.9% NaCl intravenously over 20 minutes, infused slowly to prevent hypotension.
• Methemoglobin level should be checked 30 minutes after administration.

Section Outline:

• KNOWN CYANIDE POISONING WITH SERIOUS CLINICAL EFFECTS
  • Amyl Nitrite Ampules
  • Sodium Nitrite Injection
  • Sodium Thiosulfate
• KNOWN CYANIDE EXPOSURE, BUT CLINICAL EFFECTS HAVE NOT DEVELOPED
• SUSPECTED CYANIDE POISONING
• CYANIDE TOXICITY ASSOCIATED WITH NITROPRUSSIDE INFUSION
• HYDROGEN SULFIDE POISONING

• The most common error is the failure to consider a diagnosis of cyanide poisoning.
• Amyl nitrite pearls are inefficient producers of methemoglobin; it is more important to adequately ventilate and oxygenate the patient than to administer amyl nitrite by inhalation.
• The administration of an entire ampule (10 cc) of 3% sodium nitrite to a small child may produce lethal methemoglobinemia; total hemoglobin and methemoglobin concentrations should be measured before repeating sodium nitrite to ensure that dangerous methemoglobinemia will not occur, especially in children.
• The opportunity to administer sodium thiosulfate to unconscious fire victims is commonly overlooked.
• In the presence of renal failure, thiocyanate will accumulate instead of being excreted, resulting in nausea, vomiting, and muscle aches and cramps. Hypotension and altered mental status may also develop.
• Hospitals usually stock insufficient amounts to treat more than one victim for cyanide poisoning.

Toxic effect of other substances, chiefly nonmedicinal as to source: hydrocyanic acid and cyanides.

See Also: SECTION II, Methemoglobinemia chapter; and SECTION IV, Cyanide and Hydrogen Sulfide chapters.

RECOMMENDED READING

Curry SC: Hydrogen cyanide and inorganic cyanide salts. In: Sullivan JB, Krieger GR, eds. Hazardous materials toxicology, ed 1. Baltimore, Maryland: Williams & Wilkins, 1994.

Hall AH, Rumack BH. Clinical toxicology of cyanide. Ann Emerg Med 1986;15:1067-1074.

POISINDEX Editorial Staff. Cyanide (Management/Treatment Protocol). In: Rumack BH, Hess AJ, Gelman CR, eds. POISINDEX System. Englewood, CO: MICROMEDEX, Inc. (Edition expires May 31, 1998).

Author: Luke Yip

Reviewer: Richard C. Dart