Discussion

This report demonstrates a case of methaemoglobinaemia secondary to the recreational use of ‘poppers’ presenting as altered mental state and unexplained low oxygen saturation to the emergency department.

Methaemoglobin is formed by oxidation of the haem molecule, from its reduced Fe²⁺(ferrous) state to an oxidised Fe³⁺(ferric) state via a NADPH-dependent pathway which is incapable of binding oxygen for transport. The presence of methaemoglobin in the erythrocyte structurally alters haemoglobin further affecting unaffected haem-molecules availablity for oxygen transportation by increasing affinity for oxygen which impairs oxygen off-loading to the tissues.1 Normal blood levels are 0–2%.

Methaemoglobinaemia can rarely be caused by congenital defects in the haemoglobin molecular structure and the erythrocyte metabolism.2

In an acute presentation, methaemoglobinaemia is generally acquired, secondary to the oxidising effects of exogenous substances including local anaesthetic agents (lignocaine, prilocaine), dapsone, sulphonamides and phenacetin.3–5 The primary recreational agents which cause methaemoglobinaemia are volatile nitrites (poppers) and cocaine which have been adulterated with agents such as local anaesthetics or phenacetin.6

Initially, the use of amyl nitrate was pioneered by Thomas Brunton in the nineteenth century for the treatment of angina pectoris.7

However, the volatile nitrites (particularly, isopropyl nitrite, isobutyl nitrite, butyl nitrite and amyl nitrite) have been used increasingly for the vasodilator effects, since the seventies, for recreational purposes and known as its street name ‘poppers’.8 ,9 In particular, their use is prevalent among men who have sex with men as they act as anal sphincter relaxant and heighten sexual experience.10

Diagnosis of methaemoglobinaemia is made by doing ABG analysis which typically reports normal partial pressures of oxygen and carbon dioxide, a normal ‘calculated’ haemoglobin oxygen saturation, an increased methaemogoblin concentration and, in severe cases, a metabolic acidosis.11

Conventional two wavelength pulse oximeters are not reliable to indicate the level of methaemoglobin concentration but typically there is a ‘saturation gap between the oxygen saturation on the pulse oximeter and the calculated haemoglobin oxygen saturation on the ABG.12 The ABG measures dissolved oxygen concentrations and so is unaffected by dyshaemoglobins.

In the last 10 years, newer pulse oximeters use eight wavelengths of light to measure percentage levels of methaemoglobin accurately and have been used to detect methaemoglobinia early by anaesthetists.13 ,14

In a comprehensive review, Hunter et al1 found 26 reports of methaemoglobinaemia secondary to inhalation and/or ingestion of volatile nitrites including three reported deaths. The same review found four reports of methaemoglobinaemia related to adulterants added to cocaine. Hunter et al categorised typical clinical features according to level of percentage of methaemoglobin. Our patients typified mild-to-moderate methaemoglobinaemia with central cyanosis, central not improving with oxygen administration. In cases with methemoglobinaemia levels greater than 50%, the patient typically has tachypnoea, metabolic acidosis, dysrhythmias, seizures and central nervous system depression/coma.15 Levels greater than 70% are associated with grave hypoxic symptoms and death.16

Treatment begins with securing the airway and maintaining high-flow oxygen to maximise oxygen carriage by the remaining ferrous haem. Definitive treatment is pharmacological with methylene blue which acts as a substrate for NADPH-MetHb reductase, resulting in the formation of reduced methylthioninium chloride which acts as an electron donor to reduce Fe³⁺ back to Fe²⁺. Methylene blue is provided as a 1% solution (10 mg/mL). Methylthioninium chloride is administered intravenously at a dose of 1–2 mg/kg (0.2 mL/kg of a 1% solution) over 5 min.17

Symptomatic improvement usually occurs in the first hour, but a repeat dose can be given in very severe cases. The dose can be repeated hourly as required. Although methylthioninium chloride is recommended for patients with levels greater than 30%, it was given to our patient as he was having symptomatic hypoxia.

Methylthioninium chloride should be used with caution in individuals with G6PD deficiency, which is more common in individuals of African, Asian and Mediterranean descent owing to low levels of NADPH and it may precipitate haemolysis.18