UMEM Educational Pearls

Category: Toxicology

Title: why is your patient blue? xenobiotic-induced methemoglobinemia

Keywords: methemoglobinemia, methylene blue (PubMed Search)

Posted: 5/20/2015 by Hong Kim, MD (Emailed: 5/21/2015) (Updated: 5/21/2015)
Click here to contact Hong Kim, MD

Methemoglobin (MetHb) is produce when Fe+2 in heme is oxidized to Fe+3 under oxidative stress (caused by mediation and chemicals). MetHb does not bind to oxygen and thus decrease RBC’s O2 carrying capacity.

Among medication, overdose of local anesthesia - benzocaine, dapsone, and phenazopyridine are often implicated. (Table 1)

Think about methemoglobinemia in presence of low pulse oximetry (~85%) with lack of response to supplemental oxygen, cyanosis, dyspnea, etc. (see Table 2 – signs and symptoms of MetHb) in patients who are taking or overdosed on medication listed in Table 1.

Diagnosis: CO-oximetry detects toxin-induced hemoglobinopathies, including COHb and MetHb.

Treatment: Methylene blue (1 mg/kg over 5 min) in symptomatic patients or MetHb level > 25%. Resolution of methemoglobinemia should be noted in 30 – 60 min.

G6PD deficiency: Prevalence in the U.S. is 4-7% with highest prevalence in African American population (11%). Methylene blue causes hemolytic anemia in patients with G6PD deficiency within 24 hours of administration. However, G6PD status is often unknown in ED patients.  When caring for patients with known G6PD deficiency and methemoglobinemia, providers must carefully consider the risk and benefit of treating MetHb (including severity of poisoning/MetHb) with methylene blue.

Table 1. Causes of MetHb




Benzocaine, Lidocaine, Prilocaine

Aniline dye




Organic nitrites (e.g. isobutyl nitrite)




Nitrates (well water contamination)

Quinones (Primaquine & Chloroquine)

Nitrites (food preservatives)


Silver nitrate

Nitric oxide


Amyl nitrite



Table 2. Signs and symptoms

MetHb level (%)

Signs and symptoms

1-3% (normal)


·  None


·  Low pulse oximetry (<90%)

·  Gray cutaneous coloration


·  Chocolate brown blood

·  Cyanosis


·  Dizziness, syncope

·  Dyspnea

·  Weakness

·  Headache


·  CNS depression, coma, seizure

·  Dysrhythmias

·  Tachypnea

·  Metabolic acidosis


·  Death

·  Hypoxic injury