CHAPTER 3-54: NITRITE, SODIUM, AND AMYL

Pharmacology. Sodium nitrite injectable solution and amyl nitrite crushable ampules for inhalation are components of the cyanide antidote package. The value of nitrites as an antidote to cyanide poisoning is twofold: They oxidize hemoglobin to methemoglobin, which binds free cyanide, and they may enhance endothelial cyanide detoxification by producing vasodilation. Inhalation of an ampule of amyl nitrite produces a methemoglobin level of about 5%. Intravenous administration of a single 300-mg dose of sodium nitrite in adults is anticipated to produce a methemoglobin level of about 15-20%.

Indications

1. Symptomatic cyanide poisoning. Nitrites are not usually used for empiric treatment unless cyanide is suspected very strongly, and they are not recommended for smoke inhalation victims.

2. Nitrites are possibly effective for hydrogen sulfide poisoning if given within 30 minutes of exposure.

Contraindications

1. Significant preexisting methemoglobinemia (>40%).

2. Severe hypotension is a relative contraindication because it may be worsened by nitrites.

3. Administration to patients with concurrent carbon monoxide poisoning is a relative contraindication; generation of methemoglobin may further compromise oxygen transport to the tissues. Hydroxocobalamin has supplanted nitrites for smoke inhalation victims (patients often have mixed carbon monoxide and cyanide poisoning) in countries where it is available.

Adverse effects

1. Headache, facial flushing, dizziness, nausea, vomiting, tachycardia, and sweating may occur. These side effects may be masked by the symptoms of cyanide poisoning.

2. Rapid intravenous administration may result in hypotension.

3. Excessive and potentially fatal methemoglobinemia may result.

4. Use in pregnancy. No assigned FDA category. These agents may compromise blood flow and oxygen delivery to the fetus and may induce fetal methemoglobinemia. Fetal hemoglobin is more sensitive to the oxidant effects of nitrites. However, this does not preclude their acute, short-term use for a seriously symptomatic patient (Introduction).

Drug or laboratory interactions

1. Hypotension may be exacerbated by the concurrent presence of alcohol or other vasodilators or any antihypertensive agent.

2. Methylene blue should not be administered to a cyanide-poisoned patient because it may reverse nitrite-induced methemoglobinemia and theoretically result in the release of free cyanide ions. However, it may be considered when severe and life-threatening excessive methemoglobinemia is present.

3. Binding of methemoglobin to cyanide (cyanomethemoglobin) may lower the measured free methemoglobin level.

Dosage and method of administration

1. Amyl nitrite crushable ampules. Crush one to two ampules in gauze, cloth, or a sponge and place under the nose of the victim, who should inhale deeply for 30 seconds. Rest for 30 seconds, then repeat. Each ampule lasts about 2–3 minutes. If the victim is receiving respiratory support, place the ampules in the face mask or port access to the endotracheal tube. Stop ampule use when administering intravenous sodium nitrite.

2. Sodium nitrite parenteral

   1. Adults. Administer 300 mg of sodium nitrite (10 mL of 3% solution) IV over 3–5 minutes.

   2. Children. Give 5.8-11.6 mg/kg to a maximum of 300 mg. Pediatric dosing should be based on the hemoglobin concentration if it is known (Table III–13). If anemia is suspected or hypotension is present, start with the lower dose, dilute in 50–100 mL of saline, and give over at least 5 minutes.

   3. Oxidation of hemoglobin to methemoglobin occurs within 30 minutes. If no response to treatment occurs within 30 minutes, an additional half-size dose of intravenous sodium nitrite may be given.

Formulations

1. Amyl nitrite inhalant, packaged in 0.3-mL crushable ampules, 12 per box. It is no longer a component of the conventional cyanide antidote kit (Nithiodote^®).

2. Sodium nitrite parenteral. A component of the cyanide antidote kit (Nithiodote^®), 300 mg in 10 mL of sterile water (3%), one vial per kit.

3. Suggested minimum stocking level to treat a 100-kg adult for the first 8 hours and 24 hours are two Nithiodote^®kits, containing two 300-mg vials of sodium nitrite or the equivalent as a separate stock (which is a less expensive option) plus one box of amyl nitrite inhalant ampules. Suggested for hospitals to prepare for multiple patients: two cyanide antidote kits for small hospitals, six kits for major medical centers (one kit should be kept in the emergency department). Note: Consider stocking the hydroxocobalamin antidote kit (Cyanokit^®) as an alternative antidote for cyanide poisoning.