Methaemoglobinaemia: From pathophysiology to contemporary clinical management

Methaemoglobin (MetHb) is an oxidised form of haemoglobin (Hb) unable to bind oxygen. Raised levels of MetHb reduce the blood's oxygen-carrying capacity, causing potentially severe hypoxaemia and possible death. The condition arises from three main pathologies: mutations in globin genes causing Haemoglobin-M, inherited deficiency of the enzyme cytochrome b5 reductase (CytB5R) responsible for reducing MetHb back into functional Hb, and exposure to some oxidising agents. Well-documented causative agents include dapsone and cocaine-derived anaesthetics, with emerging evidence highlighting an increasing contribution from recreational and non-prescribed exposures. As the concentration of MetHb level increases, the oxygen-carrying capacity of the blood decreases. MetHb levels are usually measured by co-oximetry. Patients are typically asymptomatic at MetHb concentrations <10% with symptoms developing as levels increase, including cyanosis, confusion, arrhythmias, coma and death. These features will present alongside misleadingly normal partial pressure of oxygen in arterial blood and arterial oxygen saturation values on arterial blood gas and will not improve with supplemental oxygen. Management depends on severity, with intravenous methylene blue remaining first-line treatment for symptomatic cases. Alternative therapies include high-dose vitamin C, exchange transfusion and potentially hyperbaric oxygen, although there is little evidence to suggest how these should be used. Due to the potentially confusing acute presentation of the condition, the diagnosis can easily be missed.