Sodium Nitrite / Sodium Thiosulfate

Pronunciation: SOE-dee-um NYE-trite/SOE-dee-um THYE-oh-SUL-fate
Class: Antidote

Trade Names

Nithiodote
- Injection, solution sodium nitrite 30 mg/mL/sodium thiosulfate 250 mg/mL

Pharmacology

Sodium nitrite

Reacts with hemoglobin to form methemoglobin, an oxidized form of hemoglobin capable of oxygen transport but with high affinity for cyanide.

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Sodium thiosulfate

Serves as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide.

Indications and Usage

For the treatment of acute cyanide poisoning that is judged to be life-threatening.

Contraindications

None well documented.

Dosage and Administration

Adults

IV Sodium nitrite 300 mg (10 mL of a 3% solution). Immediately thereafter, inject sodium thiosulfate 12.5 g (50 mL of a 25% solution). May repeat at one-half the original dose if symptoms of cyanide toxicity return.

Children

IV Sodium nitrite 6 mg/kg (0.2 mL/kg or 6 to 8 mL/m 2 of BSA of a 3% solution) not to exceed 300 mg. Immediately thereafter, inject sodium thiosulfate 250 mg/kg (1 mL/kg or approximately 30 to 40 mL/m 2 of BSA of a 25% solution), not to exceed 12.5 g. May repeat at one-half the original dose if symptoms of cyanide toxicity return.

General Advice

  • Sodium nitrite should be administered first, followed immediately by sodium thiosulfate.
  • Administration of 1 vial of each medication constitutes a single dose.
  • Administer by slow IV injection.
  • Sodium nitrite should be administered first at the rate of 2.5 to 5 mL/min, followed immediately by sodium thiosulfate.
  • The rate of infusion should be decreased if significant hypotension is noted.
  • In patients with known anemia, reduce dosage of sodium nitrite proportionately to the hemoglobin concentration.
  • Patients should be monitored for at least 24 to 48 hours after administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity.
  • Chemical incompatibility has been reported with hydroxocobalamin; do not administer simultaneously through the same IV line.

Storage/Stability

Store between 59° and 86°F. Keep from freezing. Protect from light.

Drug Interactions

Antihypertensive agents, diuretics, drugs that increase vascular nitric oxide (eg, phosphodiesterase type 5 inhibitors [eg, sildenafil])

Sodium nitrite should be used with caution with these drugs.

Adverse Reactions

Cardiovascular

Sodium nitrite

Dysrhythmia, hypotension, palpitations, syncope, tachycardia.

Sodium thiosulfate

Hypotension.

CNS

Sodium nitrite

Anxiety, coma, confusion, dizziness, fatigue, generalized numbness and tingling, headache, light-headedness, seizures, weakness.

Sodium thiosulfate

Disorientation, headache, warm sensation over body.

Dermatologic

Sodium nitrite

Diaphoresis, urticaria.

EENT

Sodium nitrite

Blurred vision.

GI

Sodium nitrite

Abdominal pain, nausea, vomiting.

Sodium thiosulfate

Nausea, salty taste in mouth, vomiting.

Hematologic

Sodium nitrate

Methemoglobinemia.

Sodium thiosulfate

Prolonged bleeding time.

Local

Sodium nitrite

Injection-site tingling.

Respiratory

Sodium nitrite

Dyspnea, tachypnea.

Miscellaneous

Sodium nitrite

Acidosis, cyanosis.

Precautions

Warnings

Life-threatening hypotension and methemoglobin formation

Sodium nitrite can cause serious adverse reactions and death in humans, even at doses less than twice the recommended therapeutic dose. Sodium nitrite causes hypotension and methemoglobin formation, which diminishes oxygen-carrying capacity. Hypotension and methemoglobin formation can occur concurrently or separately. Because of these risks, sodium nitrite should be used to treat acute life-threatening cyanide poisoning and be used with caution in patients where the diagnosis of cyanide poisoning is uncertain.

Consider alternative therapeutic approaches in patients known to have diminished oxygen or CV reserve (eg, smoke inhalation victims, preexisting anemia, cardiac or respiratory compromise), and in those at higher risk of developing methemoglobinemia (eg, congenital methemoglobin reductase deficiency) because they are at greater risk for potentially life-threatening adverse events related to the use of sodium nitrite.


Monitor

Patients should be monitored for at least 24 to 48 hours after sodium nitrite/sodium thiosulfate administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, Hgb/Hct should be obtained when treatment is initiated. It is generally recommended that methemoglobin concentrations be closely monitored and kept below 30%. Monitor BP during infusion and slow infusion rates if hypotension occurs. Monitor for an acute drop in Hct in patients with known or suspected G6PD deficiency.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Case reports in medical literature document use in pediatric patients; however, safety and efficacy have not been established. Sodium nitrite must be used with caution in patients younger than 6 mo because they may be at a higher risk of developing severe methemoglobinemia compared with older children and adults.

Renal Function

The risk of toxic reactions to these drugs may be greater in patients with impaired renal function.

Sulfite Sensitivity

Trace amounts of sodium sulfite may be present in sodium thiosulfate, but this should not deter administration of drug for treatment of emergency situations.

Anemia

Patients with anemia will form more methemoglobin than persons with normal RBC volume; use with caution.

G6PD deficiency

There is an increased risk of a hemolytic crisis with sodium nitrite administration in these patients; consider an alternative therapeutic approach.

Smoke inhalation injury

Use with caution because of the potential for worsening hypoxia because of methemoglobin formation.

Overdosage

Symptoms

Sodium nitrite

Anxiety, cardiac dysrhythmias, circulatory failure, CNS depression, CV collapse, cyanosis, dyspnea, nausea, severe hypotension, tachycardia.

Sodium thiosulfate

Reduced arterial oxygen saturation.

Patient Information

  • Sodium nitrite/sodium thiosulfate is indicated for cyanide poisoning and, in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information.
  • Inform patient of the possibility of life-threatening hypotension and methemoglobin formation.
  • Inform patients of the need for close monitoring of BP and oxygenation.

Copyright © 2009 Wolters Kluwer Health.

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