METHAEMOGLOBINAEMIA

DEFINITION

Clinical condition arising from the excessive conversion of haemoglobin to methaemoglobin, which is incapable of binding and carrying oxygen. Methaemoglobin is formed when iron in the haem molecule is oxidised from the ferrous (Fe2+) to the ferric state (Fe3+).

TOXIC CAUSES

Methaemoglobin occurs when haemoglobin is oxidised at a rate exceeding the normal enzymatic capacity for haemoglobin reduction. Certain individuals with impaired enzymatic capacity for haemoglobin reduction may be susceptible to milder oxidative stresses. Numerous agents may be responsible for this oxidation. The most frequently encountered are:

• Aniline
• Benzocaine
• Chlorates
• Chloroquine
• Dapsone
• Ground or surface water contaminated with nitrates
• Nitrates
• Nitrites
• Nitrophenol
• Phenazopyridine
• Primaquine
• Sodium nitroprusside
• 4-dimethylaminophenol

NON-TOXIC CAUSES

• Congenital enzyme deficiencies

CLINICAL FEATURES

Methaemoglobinaemia is characterised by cyanosis in the absence of cardiac or pulmonary disease, and refractory to oxygen administration. A typically greyish cyanosis is observed when levels of methaemoglobin exceed 1.5 g/dL, about 10% of the total haemoglobin in a normal individual. At this level, the patient may be otherwise asymptomatic.

Symptoms related to impaired oxygen delivery including headache, weakness, tachycardia and breathlessness develop progressively as concentrations of methaemoglobin exceed 20%. Concentrations > 50% result in severe hypoxaemia and CNS depression. Concentrations > 70% may be incompatible with life. Presence of anaemia, cardiac failure or pulmonary disease may produce symptoms of hypoxia at lower percentage levels of methaemoglobin. A blood sample of a patient with more than 15% methaemoglobinaemia has a chocolate brown colour which does not change when exposed to air.

DIFFERENTIAL DIAGNOSIS

• Sulphaemoglobinaemia.
• Cyanosis due to other causes (e.g. hypoxia)

RELEVANT INVESTIGATIONS

• Arterial blood gases. The p02 is normal while the measured oxygen saturation is decreased.
• Blood methaemoglobin concentration

Pulse oximeters are not accurate in the presence of methaemoglobinaemia.

TREATMENT

Oxygen
High flow oxygen should be administered. Identification of offending agent and prevention of further exposure. This measure alone is usually adequate for mild cases. Gastrointestinal or skin decontamination may be necessary.

Methylene blue
This specific antidote is indicated in any patient with symptoms and/or signs of hypoxia (mental changes, tachycardia, dyspnoea, chest pain). Initial dose of methylene blue: 1 to 2 mg/kg not exceeding 4 mg/kg (maximum 7 mg/kg) as a 1% solution intravenously over 5 minutes.

In cases not responding to methylene blue or where methylene blue is contraindicated (G6PD deficiency), the following measures may be considered:

• Exchange transfusion
• Hyperbaric oxygenation

CLINICAL COURSE AND MONITORING

Clinical improvement as a result of methylene blue therapy should be observed within one hour. Methaemoglobin levels should be subsequently monitored to document adequacy of response and/or recurrent methaemoglobinaemia. In these cases, further doses of methylene blue are indicated.

POTENTIAL SEQUELAE

Hypoxic organ injury if treatment is delayed or inadequate.

AUTHOR(S) / REVIEWERS

Author: Prof. Ad N.P. van Heijst, Bosch en Duin, Netherlands.
Peer Review: Cardiff 3/95; Berlin 10/95: V. Danel, T. Meredith, L. Murray, J. Pronczuk.