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Colour of blood matters: a novel aetiology for a common addiction

A 30-year-old woman presented with a 2-day history of breathlessness, cough and feeling generally unwell for 4 weeks. She had stopped smoking and had recently started flavoured electronic cigarettes (EC). On examination, she had central cyanosis and had an oxygen saturation of 85% on 15 L. Blood parameters and chest X-ray were unremarkable, and her arterial blood gas revealed a ‘chocolate’ coloured blood sample and a significant saturation gap between oxygen saturation and arterial oxygen (pH: 7.4 (7.35–7.45), Partial pressure of Oxygen (pO2): 32 kPa (11–14.4), Partial pressure of carbon-di-oxide (pCO2): 5.5 kPa (4. 6-6.4) and a methaemoglobin concentration of 18.2% (normal: ≤1.5%)). Urine toxicology screen and Glucose-6-phosphate dehydrogenase (G6PD) levels were normal. She was treated with intravenous 1% methylene blue 1 mg/kg with good outcome. A repeat arterial blood gas post treatment showed a methaemoglobin level of 2.4% and the saturation gap improved significantly. In the absence of any known aetiological factors, her use of flavoured EC (blueberry flavour containing propylene glycol) as the aetiological factor was strongly suspected. She was counselled in discontinuing its use and made an excellent recovery. She has not had any further hospital admissions and was well at her last clinic follow up. EC have been around for over a decade and remain a popular choice. Nicotine is extremely addictive but smoking is not a natural human behaviour; recent evidence suggests that EC were more effective for smoking cessation than nicotine replacement therapy when both were accompanied by behavioural support. Further trials are needed to determine if these results can be extrapolated to a worldwide population and to compare different levels of support for a stronger public health message. To increase the appeal, an option of adding flavour to the liquid from which the nicotine aerosol is generated is available with unknown short-term and long-term ill effects. As per the National Institute for Health and Care Excellence guidelines, it should be explained to patients that EC is not licensed as per current regulation, is not risk free (albeit less harmful to health than smoking) and the longterm health impact is unknown. Various EC models are available and irrespective of the design there is a lack of knowledge about the e-liquid constituents, which is the unique selling point. The liquid in EC consists of nicotine along with flavouring agents and solvents. The solvents include propylene glycol and the flavouring agents are usually aldehydes. These alcohols and aldehydes have been shown to be unstable post-formulation, forming acetyls, which have their own new toxicity profile. EC liquids containing acetyls can be chemically unstable, with reactions occurring between the solvent and flavouring components after mixing at ambient temperature. Toxicological properties from these resulting compounds differ from either of the components. Studies have shown that EC contents can lead to inflammation and airways disease, and EC-induced methaemoglobinaemia was first reported by Twohig et al. Methaemoglobinaemia is a state of altered haemoglobin where iron in the haem groups is oxidised to the ferric (Fe) state. The haemoglobin molecule is therefore unable to bind to oxygen, leading to a shift of the oxygen–haemoglobin dissociation curve to the left. The usual causes of methaemoglobinaemia can be congenital (NADH-cytochrome b5 reductase deficiency, presence of abnormal haemoglobin variants: haemoglobin M or H and G6PD) and acquired (antibiotics: trimethoprim, sulphonamides, dapsone, local anaesthetics and nitrites). The first-line treatment is supportive care and discontinuation of the implicated agent. The antidote is intravenous methylene blue (1%, 1 mg/kg) and for cases refractory to this treatment, ascorbic acid, exchange transfusion or hyperbaric oxygen may be needed. Our patient has not had any further hospital admissions in the past 6 months and at her last clinic visit (November 2020) her methaemoglobin concentration was within normal limits. She is currently using varenicline and is being followed up in community smoking cessation services. It is vital to propagate the potential ill effects associated with EC and one should consider flavoured EC as an aetiological factor in methaemoglobinaemia because the colour of the blood matters!