4 – Oral analgesic gel
Oral analgesic gel contains benzocaine, which is an oxidizing agent and a common cause of methemoglobinemia. The pictured cyanosis and classic “chocolate” blood are seen with this condition.
Background
Methemoglobinemia is a disorder of hemoglobin in which the iron atom has been oxidized from the normal Fe2+ to Fe3+. The Fe3+ iron is unable to bind to oxygen, effectively resulting in anemia and impaired oxygen delivery. Methemoglobinemia can be congenital due to enzyme deficiency, or acquired from exposure to a potent oxidizing agent. A variety of xenobiotics can act as oxidizing agents, inducing methemoglobinemia. Common agents include local anesthetics, dapsone, quinones, sulfonamides, phenazopyridine, and nitrites [1, 2].
What are the symptoms of Methemoglobinemia?
All symptoms are the result of impaired oxygen delivery to tissues and resulting end-organ dysfunction.
Signs and symptoms can include [3]:
- Cyanosis
- Chocolate brown color of arterial blood
- Low O2 saturation (usually about 85%) on pulse oximetry that does not improve with supplemental oxygen.
- Dyspnea
- Headache
- Syncope
- Coma
- Seizures
How can you diagnose methemoglobinemia?
- Regular pulse oximeters work by measuring absorption of different wavelengths of light, and since methemoglobin absorbs light differently, pulse-oximetry readings will be falsely low, usually about 85%-88%. [4]
- The most common confirmatory test for methemoglobinemia is co-oximetry (multiple-wavelength oximetry) and results are usually reported as a percentage of methemoglobin.
- Some blood gas analyzers are also able to detect methemoglobin from arterial or venous samples.
- The oxidative stress that causes methemoglobinemia can also cause hemolysis, therefore patients being evaluated for methemoglobinemia should also be evaluated for hemolytic anemia.
How do you treat methemoglobinemia?
- The primary treatment of acquired methemoglobinemia is identifying the offending agent and avoiding further exposure.
- Mild acquired methemoglobinemia is self-limited and does not require further treatment.
- Methylene blue is the antidote of choice for patients with signs and symptoms of end-organ injury from methemoglobinemia. It can reduce the Fe3+ in methemoglobin back to Fe2+.
- Exchange transfusion can be used in patients with severe methemoglobinemia.
- Vitamin C (ascorbic acid) can reduce Fe3+, but because it takes 24-48 hours to take effect, it is of limited use in patients with severe methemoglobinemia.
What are the indications and dosage for methylene blue?
- Indications
- Blood methemoglobin level > 30%
- Lower methemoglobin levels with symptoms of poor oxygen delivery including [5]:
- Altered mental status
- Ischemic chest pain
- Shortness of breath
- Signs of hypoperfusion
- Dosing
- 1 to 2 mg/kg of body weight infused intravenously over 5 minutes, followed by a 15-30 mL flush of normal saline or LR to minimize pain [6-8]
- May be repeated if cyanosis persists.
- If cyanosis persists after 2 doses, consider the possibility of G6PD deficiency. Treatment for methemoglobinemia in G6PD deficiency may consist of ascorbic acid, exchange transfusion, and hyperbaric oxygen [7, 9].
Adverse Effects of Methylene Blue
- Pain at infusion site
- Blue discoloration of urine and serum
- Interferes with pulse oximetry, resulting in falsely low readings after administration.
- Interference with laboratory studies that use light absorption.
- Can cause serotonin toxicity in combination with serotonergic medications.
- Use with caution in patients with G6PD deficiency, as methylene blue is itself an oxidizing agent and can cause hemolytic anemia in high doses.
Bedside Pearls
- Methemoglobinemia results from oxidation, or loss of an electron, of the iron atom in hemoglobin.
- Methemoglobinemia can be induced by medications such as
- Local anesthetics
- Dapsone
- Quinones
- Sulfonamides
- Phenazopyridine
- Ntrites
- Symptoms include cyanosis, pulse oximetry reading in mid-80’s that does not improve with supplemental oxygen, shortness of breath, and altered mental status.
- Methylene blue is the first-line treatment for severe methemoglobinemia.