Management
Treatment pathway
If there are any concerns about treatment, contact the National Poisons Information Service.
A guide to treatment is as follows:
* Dextrose – there is no trial evidence per say for the use of intravenous Dextrose but it’s use is well described and biologically sound; both NADH and NADPH are produced by the metabolism of glucose [1].
Other therapeutic options including high dose ascorbic acid, cytochrome P450 inhibitors, and N-acetylcysteine have been proposed but there is as yet insufficient robust evidence to recommend their use [7, 8].
Methylene Blue [5,9]
Methylene Blue is an aromatic dye found in the antidote cupboard of the ED.
Action: Acts as a co-factor in a MetHb reducing reaction. NADPH-methaemoglobin-reductase reduces Methylene Blue to Leukomethylene blue, which in turn reduces Fe3+ to Fe2+. Thus this pathway, which only plays a minor role in health, can be exploited to become the main therapeutic target in methaemoglobinaemia.
Administration: 1-2 mg/kg iv over 3-5 minutes
Response: Effects should be seen quickly with a dramatic reduction in MetHb in < 30 minutes.
If required further doses can be given after 30 minutes (discuss doses over 4mg/kg with local poisons service)
Monitoring: Methylene Blue interferes with pulse oximetry so SpO2 will appear to fall with treatment (and can go as low as 65%). Monitoring is by co-oximeter measurement of MetHb and SaO2.
Side effects: Nausea and vomiting, blue urine, diaphoresis, restlessness, anaphylaxis, pulmonary hypertension, serotonin syndrome and haemolytic anaemia are reported.
Caveats and cautions to consider :
Dosage: Methylene Blue is actually an oxidative agent. In high doses the oxidative effects of Methylene Blue overcome the reductive effects of Leukomethylene blue and increase MetHb.
NADPH reductase and G6PD deficiency: Methylene Blue works via the NADPH pathway so will have no effect in patients with NADPH-methaemoglobin-reductase deficiency and limited effect in G6PD deficiency (G6PD catalyses the formation of NADPH). There are also documented reports of Methylene Blue causing haemolytic anaemia in G6PD deficiency [10].
Chlorate poisoning: Chlorate can inactivate G6PD.
M Haemoglobin: Methylene Blue has limited effect in patients with M Haemoglobin.
Sulfhaemoglobinaemia: MetHb can be been further modified by binding irreversibly to sulphur to form Sulfhaemoglobin (SulfHb). This happens with exposure to certain toxins, notable examples being Sulfasalazine and Sumatriptan. Clinically the presentation is similar. Patients may have a green tinge to their blood on venepuncture. There is no specific treatment. Sulfhaemoglobinaemia does not respond to Methylene Blue
Pregnancy: Very limited data exists but the general consensus is that the risks of treatment with Methylene Blue are less than withholding treatment if it is clinically indicated. Women should be counselled about the risks and benefits and have fetal monitoring throughout.