Sodium Nitrite - Uses, Dose, Side effects

Sodium Nitrite promotes the formation of methemoglobin which then competes with cytochrome oxidase for the cyanide ion.

Sodium nitrite Uses:

  • Cyanide poisoning:
    • Treatment of acute, life-threatening cyanide poisoning.

Note:

  • The preferred antidote for the treatment of acute cyanide poisoning is hydroxocobalamin, especially in patients who have concurrent carbon monoxide poisoning (eg, smoke inhalation), significant anemia, or G6PD deficiency.
  • Sodium nitrite in combination with sodium thiosulfate should be considered only if hydroxocobalamin is unavailable, there is a contraindication to the use of hydroxocobalamin, or if the patient has a known sensitivity to hydroxocobalamin or vitamin B analogs.

Sodium Nitrite Dose in Adults

Sodium Nitrite Dose in the treatment of Cyanide poisoning: 

When someone has cyanide poisoning, sodium nitrite can help. It's given through an IV, usually along with sodium thiosulfate. First, doctors give sodium nitrite, then right after, they give sodium thiosulfate. The initial dose of sodium nitrite is 300 mg (which is 10 mL of a 3% solution). If the symptoms come back, they might give half of that dose again.

Doctors keep an eye on a person's methemoglobin levels. If those levels go above 30%, they stop giving sodium nitrite.

For some people who can't handle high methemoglobin levels (like those with heart or lung problems), doctors might base the dose on their hemoglobin levels. They can quickly check these levels at the bedside. Here's how the dose works based on hemoglobin levels:

  • If hemoglobin is 7 g/dL, the dose is 0.19 mL/kg.
  • If it's 8 g/dL, the dose is 0.22 mL/kg.
  • If it's 9 g/dL, the dose is 0.25 mL/kg.
  • And so on, up to 14 g/dL, where the dose is 0.39 mL/kg.

After giving the treatment, doctors watch the patient closely for 24 to 48 hours. If the symptoms come back during this time, they might repeat the treatment at half the original dose.

Sodium Nitrite Dose in Childrens

Sodium Nitrite Dose in the treatment of Cyanide poisoning:

  • When treating cyanide poisoning with sodium nitrite through an IV, the typical dose is 6 mg per kilogram of body weight.
  • This translates to 0.2 mL per kilogram or 6-8 mL per meter squared of a 3% solution.
  • The maximum dose is 300 mg or 10 mL of a 3% solution. If the symptoms of cyanide toxicity return, the treatment may be repeated at half the original dose.

It's important to give sodium nitrite alongside sodium thiosulfate, with sodium nitrite administered first followed immediately by sodium thiosulfate.

Doctors keep an eye on methemoglobin levels, and if they go above 30%, they stop giving sodium nitrite.

For patients who can't handle high methemoglobin levels due to conditions like heart or lung disease, doctors refer to adult dosing.

After administering the treatment, patients are monitored closely for 24-48 hours. If symptoms return during this time, the treatment may be repeated at half the original dose.

Pregnancy Risk Factor C

  • Sodium nitrite poses a Pregnancy Risk Factor C, meaning there are potential risks to the fetus if a pregnant woman is exposed to high levels.
  • While animal studies haven't shown teratogenic effects (effects on fetal development), they have shown other negative impacts.
  • One concern is that the fetus has lower levels of methemoglobin reductase, which could lead to issues like prenatal hypoxia caused by nitrite exposure.
  • However, if a pregnant woman needs an antidote that includes sodium nitrite due to a clear medical need, it shouldn't be withheld solely out of fear of harming the fetus.
  • Instead, doctors should weigh the risks and benefits carefully.

Use during breastfeeding:

  • It's uncertain whether sodium nitrite passes into breast milk.
  • Because of this uncertainty, the manufacturer advises caution when giving sodium nitrite to breastfeeding women.
  • This caution is because any substance that enters breast milk can potentially affect the nursing infant.

Sodium Nitrite Dose in Kidney Disease:

  • The manufacturer's labeling doesn't specify any dosage adjustments for sodium nitrite based on kidney function.
  • However, it's important to note that sodium nitrite is mainly eliminated through the kidneys, so patients with renal impairment might be at higher risk of experiencing adverse effects.

Sodium Nitrite Dose in Liver disease:

  • The manufacturer's labeling does not provide any specific dosage adjustments for sodium nitrite in patients with hepatic impairment.
  • This is because there haven't been studies specifically addressing the use of sodium nitrite in individuals with liver problems.

Side effects of Sodium Nitrite:

  • Cardiovascular:
    • Cardiac Arrhythmia
    • Flushing
    • Hypotension
    • Palpitations
    • Syncope
    • Tachycardia
  • Central Nervous System:
    • Anxiety
    • Coma
    • Confusion
    • Dizziness
    • Fatigue
    • Headache
    • Numbness
    • Paresthesia
    • Seizure
    • Tingling Sensation (At Injection Site)
  • Dermatologic:
    • Diaphoresis
    • Urticaria
  • Endocrine & Metabolic:
    • Acidosis
  • Gastrointestinal:
    • Abdominal Pain
    • Nausea
    • Vomiting
  • Hematologic & Oncologic:
    • Methemoglobinemia
  • Neuromuscular & Skeletal:
    • Weakness
  • Ophthalmic:
    • Blurred Vision
  • Respiratory:
    • Cyanosis
    • Dyspnea
    • Tachypnea

Contraindications to Sodium nitrite:

  • The manufacturer's labeling for sodium nitrite does not list any contraindications, meaning there are no specific situations where its use is strictly prohibited.
  • However, caution should still be exercised, especially in patients with certain medical conditions or risk factors, such as renal or hepatic impairment.

Warnings and Precautions

Hypotension: [US Boxed Warning]:

  • Sodium nitrite carries a serious warning about causing severe hypotension, which can reduce the ability of blood to carry oxygen.
  • Even doses lower than double the recommended therapeutic dose can lead to significant adverse effects.
  • Healthcare providers need to closely monitor patients for proper blood flow and oxygen levels, ensuring they have a normal amount of fluid in their bodies.
  • Sodium nitrite should be used cautiously in patients where cyanide poisoning isn't certain, those with existing low oxygen levels or heart issues (like smoke inhalation victims, anemia, or significant blood loss), and those who might be harmed by vasodilation.
  • In such cases, hydroxocobalamin might be a safer alternative.

Methemoglobinemia: [US Boxed Warning]:

  • Sodium nitrite carries a serious warning about causing methemoglobin formation, which reduces the blood's ability to carry oxygen.
  • Even doses lower than double the recommended therapeutic dose can lead to significant adverse effects.
  • Healthcare providers must monitor patients closely for adequate blood flow and oxygen levels.
  • Sodium nitrite should be used cautiously in cases where cyanide poisoning isn't certain, in patients with existing low oxygen levels or heart issues (like smoke inhalation victims, anemia, or significant blood loss), and in patients at higher risk for developing methemoglobinemia (like those with congenital methemoglobin reductase deficiency).
  • Hydroxocobalamin might be a safer alternative in such cases.
  • Additionally, caution should be exercised when sodium nitrite is used with other medications known to cause methemoglobinemia, such as nitroglycerin or phenazopyridine.
  • If methemoglobin levels exceed 30%, sodium nitrite should be stopped.
  • In severe cases of methemoglobinemia, intravenous methylene blue or exchange transfusion may be necessary for treatment.

Anemia:

  • When administering sodium nitrite to patients with anemia, caution is advised because these patients are more likely to develop methemoglobin.
  • Methemoglobin is a form of hemoglobin that cannot carry oxygen effectively.
  • To mitigate this risk, healthcare providers may recommend reducing the dosage of sodium nitrite based on the patient's oxygen-carrying capacity, which is typically affected by the severity of their anemia.
  • By adjusting the dosage in proportion to the patient's oxygen-carrying capacity, the risk of methemoglobin formation can be minimized while still providing the necessary treatment for cyanide poisoning.

Glucose-6-phosphate dehydrogenase deficiency:

  • Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency face a higher risk of experiencing a hemolytic crisis after receiving sodium nitrite.
  • In such cases, healthcare providers should explore alternative treatment options if available.
  • It's crucial to monitor these patients closely for any sudden decrease in hematocrit levels, as this could indicate a hemolytic crisis.
  • In severe cases, an exchange transfusion may be necessary to manage the hemolysis effectively.

Renal impairment:

  • Given that sodium nitrite is significantly eliminated through the kidneys, it's important to exercise caution when using it in patients with renal impairment.
  • Because of the potential for adverse events to increase in these patients, healthcare providers should be vigilant when prescribing sodium nitrite and closely monitor for any signs of adverse reactions.
  • Adjustments to the dosage or frequency of administration may be necessary in individuals with renal impairment to minimize the risk of complications.

Sodium nitrite: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)

Alfuzosin

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Antipsychotic Agents (Second Generation [Atypical])

Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).

Barbiturates

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Benperidol

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Blood Pressure Lowering Agents

May enhance the hypotensive effect of HypotensionAssociated Agents.

Brimonidine (Topical)

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Dapsone (Topical)

May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents.

Diazoxide

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

DULoxetine

Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.

Herbs (Hypotensive Properties)

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Hypotension-Associated Agents

Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.

Levodopa-Containing Products

Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.

Local Anesthetics

Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased.

Lormetazepam

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Methemoglobinemia Associated Agents

May enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia.

Molsidomine

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Naftopidil

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Nicergoline

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Nicorandil

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Nitric Oxide

May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine.

Nitroprusside

Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.

Pentoxifylline

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Pholcodine

Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.

Phosphodiesterase 5 Inhibitors

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Prilocaine

Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents.

Prostacyclin Analogues

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Quinagolide

May enhance the hypotensive effect of Blood Pressure Lowering Agents.

Risk Factor D (Consider therapy modification)

Amifostine

Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.

Obinutuzumab

May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.

Risk Factor X (Avoid combination)

Bromperidol

Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.

Monitoring parameters:

  • Duration: Monitor the patient for at least 24 to 48 hours after administration.
  • Blood Pressure and Heart Rate: Continuously monitor blood pressure and heart rate during and after the infusion of sodium nitrite.
  • Hemoglobin/Hematocrit: Regularly check hemoglobin and hematocrit levels to assess oxygen-carrying capacity.
  • Co-Oximetry: Use co-oximetry to measure various forms of hemoglobin, including methemoglobin and oxyhemoglobin.
  • Serum Lactate Levels: Monitor serum lactate levels to evaluate tissue oxygenation and metabolism.
  • Venous-Arterial PO Gradient: Assess the venous-arterial PO gradient to determine tissue oxygen delivery.
  • Serum Methemoglobin and Oxyhemoglobin: Measure serum levels of methemoglobin and oxyhemoglobin to monitor for methemoglobinemia.
  • Pretreatment Cyanide Levels: Pretreatment cyanide levels may help in diagnosis, but if the patient is critically ill, do not delay sodium nitrite therapy while waiting for laboratory results.

How to administer Sodium nitrite?

Administration of Sodium Nitrite via IV:

  • Speed: Administer slowly through IV injection at a rate of 2.5 to 5 mL per minute.
  • Timing: Initiate administration as soon as possible after diagnosing acute, life-threatening cyanide poisoning.
  • Follow-Up: Immediately follow sodium nitrite administration with the administration of sodium thiosulfate.
  • Hypotension: If significant hypotension occurs, decrease the rate of infusion accordingly to manage the condition effectively.

Mechanism of action of Sodium nitrite:

  • Sodium nitrite triggers the formation of methemoglobin, a form of hemoglobin.
  • Methemoglobin then competes with cytochrome oxidase for the cyanide ion in the bloodstream.
  • When cyanide combines with methemoglobin, it forms cyano methemoglobin.
  • This process frees up cytochrome oxidase, an enzyme crucial for aerobic metabolism.
  • By freeing cytochrome oxidase, sodium nitrite enables aerobic metabolism to continue despite the presence of cyanide in the body.

Onset and Peak Effect:

  • Methemoglobinemia: The onset of methemoglobinemia typically occurs within 30 to 60 minutes after administration of sodium nitrite, reaching its peak effect during this time.

Duration of Action:

  • Methemoglobinemia: The duration of action for methemoglobinemia induced by sodium nitrite is approximately 55 minutes.

Metabolism:

  • Sodium nitrite is metabolized in the body to various metabolites, including ammonia.

Excretion:

  • Sodium nitrite is primarily excreted in the urine, with approximately 40% being eliminated unchanged in its original form.

International Brands of Sodium nitrite:

  • Sodium Nitrite Injection

Sodium nitrite Brand Names in Pakistan:

No Brands Available in Pakistan.

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