Methemoglobinemia & Methylene Blue

Hemoglobin iron normally exists in the reduced ferrous state ($Fe^{2+}$), which binds molecular oxygen reversibly. Oxidizing exposures strip an electron from ferrous iron, converting it into the ferric state ($Fe^{3+}$) to form methemoglobin (MetHb). Ferric iron is incapable of binding oxygen. Furthermore, the presence of ferric iron in one subunit alters hemoglobin's tetrameric conformation, increasing the oxygen affinity of the remaining ferrous subunits and shifting the oxyhemoglobin dissociation curve to the far left, severely impairing oxygen release to tissues.

Under basal conditions, endogenous NADH-cytochrome b5 reductase (methemoglobin reductase) continuously reduces MetHb back to normal hemoglobin, keeping baseline MetHb levels $< 1\%$. An alternative secondary pathway utilizing NADPH-methemoglobin reductase exists but requires an exogenous electron acceptor—such as methylene blue—to function.

Standard commercial pulse oximeters calculate $SpO_2$ by measuring light absorbance at two wavelengths: 660 nm (red) and 940 nm (infrared). Methemoglobin has high optical absorbance at both 660 nm and 940 nm, producing an absorbance ratio of 1.0. The pulse oximeter microprocessor interprets this 1.0 ratio as a fixed oxygen saturation of approximately 85%, regardless of actual arterial oxygenation or true methemoglobin fraction. Diagnosis mandates an arterial or venous blood gas with co-oximetry, which directly measures light absorption across multiple distinct wavelengths to quantify exact percentages of oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin, and methemoglobin.