Makindo Medical Notes.com

Related Subjects: |Methylthioninium chloride (Methylene blue) |Methaemoglobinaemia |Drug Toxicity with Specific Antidotes

Pulse oximetry can under and overestimate oxygen saturation. Unlike normal haemoglobin, methaemoglobin is unable to effectively release oxygen to body tissues, which can lead to symptoms of oxygen deprivation.

About

• A life threatening cause of tissue hypoxia
• Due to Iron losing electrons (Oxidation) so Fe²⁺ → Fe³⁺
• Fe³⁺ (ferric) iron cannot bind and transport oxygen.
• Caused by oxidizing agents

Aetiology

• The Hb of a red blood cell the haem group contains an iron molecule in the reduced or ferrous form (Fe²⁺). In this form, iron can combine with oxygen, by sharing an electron, to form oxyhaemoglobin. When haemoglobin is oxidised, it is converted to the ferric state (Fe³⁺) or methaemoglobin which lacks the electron needed to form a bond with oxygen.
• Therefore MetHb is incapable of oxygen transport. Because red blood cells are continuously exposed to various oxidant stresses, blood normally contains approximately 1% methaemoglobin levels. Methaemoglobin reductase (NADH dependant b 5 reductase) catalyses the reduction of Methaemoglobin to Haemoglobin

Precipitant

• Oxidizing agents: dapsone, phenacetin, sulphonamides, aniline dyes, lidocaine, nitrites and nitrates.
• Congenital methaemoglobinemia due to cytochrome b5 reductase deficiency is very rare
• Haemoglobin M disease, a mutation in the gene coding for one of the globin proteins

Clinical

• Cyanosed patient, SOB, Anxiety, seizures, coma
• Pulse oximetry can under and overestimate oxygen saturation
• 100% oxygen should be administered in significant cases
• Known or suspected G6PD deficiency is a contraindication to the use of methylene blue

Investigations

• CXR, FBC, U&E, Lactate
• ABG: Chocolate brown arterial blood that does not become red with exposure to air. ABG will reveal a normal arterial oxygen tension (PO₂) and a metabolic acidosis proportional to the severity and duration of tissue hypoxia

Methaemoglobin levels

• < 1% Normal range
• 3-5% slight skin discolouration
• 15-20% cyanosis but no symptoms
• 25-50% breathless cyanosed headache
• 50% confusion is due to the oxidation of Fe²⁺ to Fe³⁺

Methylene blue is a MAOI and, when administered to a patient taking any other serotonergic drug, can lead to serotonin syndrome. Methylene blue should be used cautiously and judiciously in infants and patients with G6PD-deficiency, but is not contraindicated.

Management

• ABC, 100% O₂, ITU. ABC management with high flow O₂.
• Adult: Methylthioninium chloride (methylene blue): Initially 1–2 mg/kg over 5 mins, then 1–2 mg/kg after 30–60 minutes if required, seek advice from National Poisons Information Service if further repeat doses are required; maximum 7 mg/kg per course. Methylthioninium chloride by the intravenous route is approved only for drug-induced methaemoglobinaemia in adults. It should be avoided in patients who have been treated recently with serotonergic antidepressants, including SSRIs, clomipramine, and venlafaxine. If use cannot be avoided, the lowest possible dose should be used and the patient observed closely for CNS effects for up to 4 hours after administration. If features of CNS toxicity develop after use of methylthioninium, the patient should be monitored closely and given supportive care.
• Child 3 months–17 years: Methylthioninium chloride: Initially 1–2 mg/kg, then 1–2 mg/kg after 30–60 minutes if required, to be given over 5 minutes, seek advice from National Poisons Information Service if further repeat doses are required; maximum 7 mg/kg per course.
• ABG analysis will typically reveal a normal arterial oxygen tension (PO₂) and a metabolic acidosis proportional to the severity and duration of tissue hypoxia
• Aggressive medical therapy, including administration of methylene blue, should be considered for patients with overt signs of tissue hypoxia (not just cyanosis). Methylene blue is an exogenous electron donor and so reduces Fe3+ to Fe2+
• Known or suspected G6PD deficiency is a contraindication to the use of methylene blue

References

• Methaemoglobinaemia