Medicine and Man

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Hemoglobin contains 4 heme groups and each heme group contains Fe2+

When Fe2+ gets oxidized to Fe3+ it is called MetHb

MetHb not only reduces the oxygen binding capacity of Hb but interferes with oxygen unloading to the tissues thereby shifting the oxygen dissociation curve to the left

Under physiologic conditions MetHb is continuously produced due to the oxidizing effect of oxygen but is reduced back to Hb by cytochrome b5 reductase (NADPH MetHb reductase)

Normal levels of MetHb in humans < 2%

5 g/dl of deoxyHb produces cyanosis

MetHb produces cyanosis at 1.5 g/dl

Most commonly caused by drugs:

Pulse oximetry & Co-oximetry

Regular pulse oximeter measures UV absorption only 2 wavelengths for oxyHb (940nm) and deoxyHb (660)

Co-oximeter measures light absorption of blood at multiple UV wavelengths

They can measure the percentages of oxyHb, deoxyHb, carboxyHb and MetHb

Require a blood sample – cannot be used for continuous monitoring

Pulse oximeter is unreliable for measuring MetHb because methemoglobin is detected by both the oxyHb (940 nm) and deoxyHb (660 nm) sensors of the oximeters

At low levels (20%), methemoglobin is detected primarily by the deoxyHb sensor,and a pulse oximeter may show a falsely low oxygen saturation

At high methemoglobin levels (70%), detection by the oxyhemoglobin sensor pre- dominates, and a pulse oximeter may show a falsely high reading

Methylene blue, the antidote for MetHb, is also detected by the pulse oximeter’s deoxyHb sensor, which leads to the potential for falsely low post-treatment oxygen saturation readings

Clinical findings

Cyanosis unresponsive to oxygen

Cyanosis in the presence of normal (calculated) oxygen saturation

Saturation gap = Calculated sat – pulse oxymetry

Suspect presence of abnormal Hb if the saturation gap > 5% (+ or -)

Saturation gap is not proportional to MetHb level

Treatment

Symptomatic and those with MetHb > 20% should receive methylene blue

Methylene blue acts as a cofactor for NADPH MetHb reductase thereby converting Fe3+ to Fe2+ in Hb

Methylene blue is not effective in patients with G6PD deficiency as they have very low levels of NADPH – will cause hemolysis

Side effects of methylene blue includes bluish skin which may complicate assessment of cyanosis

Methylene blue also causes MetHb (in higher doses) !!!!!

If not responding to methylene blue – ? sulfHb, ongoing toxicity esp if toxin is ingested or G6PD deficiency – you may also have to consider an alternative diagnosis !!!

Rarely hyperbaric oxygen and/or exchange transfusion may be done