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[Conditions](https://durgical.com/en/conditions/) · [Metabolism: heme, bilirubin and iron](https://durgical.com/en/conditions/)

# Methemoglobinemia

Excess hemoglobin with oxidised iron, which cannot carry oxygen; it causes cyanosis that does not improve with oxygen and chocolate-coloured blood.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Skin](https://durgical.com/en/anatomy/skin/)
- [White matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/)

## In biochemistry

- [Spectrophotometry and colorimetry (Beer–Lambert law)](https://durgical.com/en/biochemistry/topics/spectrophotometry-and-colorimetry/)
- [Nitric oxide (NO)](https://durgical.com/en/biochemistry/molecules/nitric-oxide/)
- [Heme](https://durgical.com/en/biochemistry/molecules/heme/)
- [Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)](https://durgical.com/en/biochemistry/topics/hemoglobin-variants/)
- [Oxygen binding: haemoglobin versus myoglobin](https://durgical.com/en/biochemistry/topics/oxygen-binding-haemoglobin-versus-myoglobin/)

## In the clinical exam

- [Pulse oximetry](https://durgical.com/en/clinical-exam/pulse-oximetry/)

## In physiology

- [Oxygen transport and the dissociation curve](https://durgical.com/en/physiology/oxygen-transport-and-the-dissociation-curve/)
- [Oxygenation: SpO₂, PaO₂, cyanosis and oxygen therapy](https://durgical.com/en/physiology/oxygenation-spo-pao-cyanosis-and-oxygen-therapy/)
- [Carbon monoxide, methemoglobin and cyanide](https://durgical.com/en/physiology/carbon-monoxide-methemoglobin-and-cyanide/)

## What it is

A rise in methemoglobin (heme iron in the Fe³⁺ state) above normal (1–2 %), acquired from oxidants or congenital.

## Who gets it

The acquired form is the most common: topical local anaesthetics, dapsone and nitrites. In Colombia primaquine for P. vivax malaria and nitrate-rich well water in infants are causes to keep in mind.

## Causes

- Oxidant drugs: topical benzocaine and lidocaine, dapsone, primaquine, nitrates, rasburicase
- Chemicals: nitrites, anilines, nitrobenzene
- Congenital: cytochrome b5 reductase deficiency (CYB5R3) or M hemoglobins (abnormal globin)

## Risk factors

- Infants under 6 months (less cytochrome b5 reductase, more oxidisable HbF)
- G6PD deficiency
- Procedures with topical mucosal anaesthesia (endoscopies)

## Pathophysiology

Fe³⁺ does not bind O₂ and also raises the affinity of the other hemes in the tetramer: the curve shifts left and less oxygen is delivered. Normally cytochrome b5 reductase (with NADH) returns the iron to Fe²⁺; a backup NADPH pathway is the one methylene blue activates.

## Symptoms and signs

- Grey-blue cyanosis that does not improve with oxygen
- Headache, dizziness and fatigue
- Breathlessness and tachycardia
- Chocolate-coloured blood

## Red flags

- Methemoglobin above 30 % or signs of ischaemia (chest pain, acidosis)
- Confusion, seizures or coma

## Diagnosis

**Clinical**
Cyanosis with normal PaO₂ and pulse-oximetry saturation around 85 % that does not change with oxygen, after an oxidant drug or chemical.

**Tests**
Co-oximetry (measures methemoglobin directly); arterial gases with normal PaO₂ (saturation gap); lactate; G6PD before methylene blue; cytochrome b5 reductase activity and hemoglobin electrophoresis in congenital cases.

**Imaging**
Does not contribute to diagnosis; [chest](https://durgical.com/en/anatomy/region/chest/) X-ray rules out lung causes of cyanosis.

## Treatment

**Acute**
Stopping the oxidising agent and giving oxygen

**Medical**
Intravenous methylene blue in symptomatic or high-level cases (contraindicated in G6PD deficiency)

**Medical**
Ascorbic acid or exchange transfusion when methylene blue cannot be used

**Procedure**
Hyperbaric oxygen in severe refractory cases

## Drugs for this condition

- [Methylthioninium chloride (methylene blue)](https://durgical.com/en/pharmacology/methylthioninium-chloride/)

## Complications

- Myocardial ischaemia and arrhythmias
- Lactic acidosis
- Hemolysis (especially with G6PD deficiency)

## Prognosis

Excellent if recognised and treated promptly; congenital type I causes only cyanosis.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does the pulse oximeter read about 85 % in methemoglobinemia?

Methemoglobin absorbs both wavelengths the device uses equally; co-oximetry gives the true value.

## How does methylene blue work?

Using NADPH (from the pentose pathway) it reduces Fe³⁺ to Fe²⁺ via NADPH-dependent methemoglobin reductase.

## When is methylene blue contraindicated?

In G6PD deficiency: there is not enough NADPH, it fails and can cause hemolysis.

## Which way does methemoglobin shift the oxygen dissociation curve?

To the left: the remaining hemes release less oxygen to the tissues.

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## Related conditions

- [Sickle cell disease](https://durgical.com/en/conditions/sickle-cell-disease/)
- [Malaria](https://durgical.com/en/conditions/malaria/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Methemoglobinemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000562.htm) (MedlinePlus, US National Library of Medicine, 2026); [CYB5R3 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/cyb5r3/) (MedlinePlus, US National Library of Medicine, 2026); [Methemoglobinemia, beta-globin type: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/methemoglobinemia-beta-globin-type/) (MedlinePlus, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/conditions/methemoglobinemia/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/methemoglobinemia/