Methemoglobinemia
Methemoglobinemia is oxidation of hemoglobin iron from the ferrous (Fe2+) to the ferric (Fe3+) state, producing cyanosis unresponsive to supplemental oxygen, chocolate-brown blood, and a saturation gap between a low pulse oximetry reading and a normal PaO2. Diagnosis is confirmed by co-oximetry measuring the methemoglobin level, and symptomatic or high-level disease is treated with methylene blue, which is avoided in glucose-6-phosphate dehydrogenase deficiency.
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
Definition: methemoglobinemia is oxidation of hemoglobin iron from the normal ferrous (Fe2+) state to the ferric (Fe3+) state, forming methemoglobin, which cannot bind oxygen.
- Epidemiology
Acquired disease predominates: the great majority of cases are drug- or toxin-induced rather than congenital, occurring at any age when an oxidizing exposure is given.
- Risk factors
Exposure to an oxidizing drug or chemical: the dominant risk factor; local anesthetics ending in "-caine" (benzocaine, lidocaine, prilocaine), dapsone, nitrites and nitrates, sulfonamides, and aniline dyes are the classic culprits.
- Pathophysiology
Oxidation of the heme iron: an oxidizing agent (dapsone, benzocaine, nitrites, aniline dyes) strips an electron from the ferrous iron of heme, converting it to the ferric state and forming methemoglobin.
- Clinical features
Cyanosis unresponsive to supplemental oxygen: a slate-gray or bluish discoloration of the skin and mucous membranes that fails to improve with high-flow oxygen, the hallmark that distinguishes this from ordinary hypoxemia.
- Differential diagnosis
Hypoxemic respiratory failure: cyanosis with a genuinely low PaO2 and abnormal lung findings or imaging, distinguished by the low (not normal) PaO2.
- Diagnosis
Confirm with co-oximetry measuring the methemoglobin fraction directly: a multi-wavelength co-oximeter (run on an arterial or venous blood gas sample) reports the percentage of total hemoglobin that…
- Management
Stop the offending oxidizing agent immediately and remove any topical source (wipe off residual anesthetic gel or spray) as the first action in every case.
- Complications
Severe tissue hypoxia and end-organ injury: myocardial ischemia, seizures, and coma at high methemoglobin levels from critically reduced oxygen delivery, up to death at levels near 50% to 70%.
- Prognosis
Excellent with prompt recognition and treatment: acquired disease typically resolves quickly once the agent is stopped and methylene blue or ascorbic acid is given, with most patients recovering fully.
- Prevention
Avoid or limit topical benzocaine-containing spray anesthetics before endoscopy, bronchoscopy, or transesophageal echocardiography, using the lowest effective amount for the shortest necessary application rather than repeated sprays.
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy that leaves red cells unable to buffer oxidative stress, producing episodic intravascular hemolysis with bite cells and Heinz bodies after infection, fava beans, or oxidant drugs. Diagnosis rests on a G6PD enzyme activity assay that can be falsely normal during the acute episode and must be repeated 2 to 3 months later, while management centers on trigger avoidance, supportive care, and transfusion for severe hemolysis.
- Carbon monoxide poisoning
Carbon monoxide poisoning follows inhalation of a colorless, odorless combustion product that binds hemoglobin roughly 200 to 300 times more avidly than oxygen, producing tissue hypoxia that pulse oximetry cannot detect. Diagnosis requires co-oximetry on a blood gas to measure carboxyhemoglobin. Treatment is immediate high-flow 100% oxygen, escalated to hyperbaric oxygen for loss of consciousness, neurologic or cardiac ischemia, or pregnancy.