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Severe acquired methaemoglobinaemia in glucose-6-phosphate dehydrogenase deficiency — SCE Respiratory MCQ

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HardHypoxaemiaSevere acquired methaemoglobinaemia in glucose-6-phosphate dehydrogenase deficiencySCE Respiratory

A 63-year-old man with granulomatosis with polyangiitis is receiving rituximab and glucocorticoids. Because of a previous severe reaction to co-trimoxazole, dapsone was started for Pneumocystis jirovecii prophylaxis 10 days ago. He presents with headache, central chest discomfort and progressive cyanosis. He is confused but protecting his airway. Respiratory rate is 28 breaths/min, blood pressure 138/76 mmHg and pulse 112 beats/min. His SpO₂ remains 85% despite oxygen at 15 L/min through a reservoir mask. Chest radiography is clear. Arterial blood gas analysis on oxygen shows pH 7.43, PaCO₂ 4.3 kPa, PaO₂ 38 kPa and a calculated oxygen saturation of 100%. The arterial sample is chocolate-brown, and multiwavelength co-oximetry shows a methaemoglobin fraction of 43%. His haemoglobin is 118 g/L, compared with 136 g/L one week earlier, and the blood film shows bite cells. ECG demonstrates widespread ST-segment depression. Review of records identifies previously documented severe glucose-6-phosphate dehydrogenase deficiency. Dapsone is discontinued and supportive high-concentration oxygen is continued. Which definitive treatment should now be prioritised?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: C — Therapeutic whole-blood exchange

Explanation lettering: E = shown as B · D = shown as C · C = shown as D · B = shown as E

The refractory pulse-oximeter reading near 85%, very high PaO₂, falsely normal calculated saturation and chocolate-brown blood identify dyshemoglobinaemia rather than pulmonary gas-exchange failure. Co-oximetry confirms severe methaemoglobinaemia. Confusion, myocardial ischaemia and a methaemoglobin fraction of 43% require urgent definitive treatment. Methylthioninium chloride is normally first-line for symptomatic methaemoglobinaemia, but it requires NADPH generated through the G6PD-dependent pathway. It is contraindicated in G6PD deficiency because it may be ineffective and can exacerbate oxidative haemolysis. Therapeutic whole-blood exchange should therefore be prioritised; it removes oxidised erythrocytes and replaces them with functional haemoglobin and is an accepted salvage strategy when methylthioninium chloride is contraindicated or ineffective. A is the usual first-line antidote but is specifically excluded here. B may be appropriate for clinically important haemolytic anaemia, but his modest haemoglobin fall does not address the immediately life-threatening proportion of dysfunctional haemoglobin as effectively as exchange. C can increase dissolved oxygen and has been used as rescue treatment, but evidence is limited and it does not directly replace the oxidised erythrocyte mass. E is inappropriate while he protects his airway: ventilation cannot correct haemoglobin oxidation, and his PaO₂ is already markedly elevated.

Reference: BTS Guideline for oxygen use in adults in healthcare and emergency settings (2017) — https://www.brit-thoracic.org.uk/document-library/guidelines/emergency-oxygen/bts-guideline-for-oxygen-use-in-adults-in-healthcare-and-emergency-settings/ Methylthioninium chloride Proveblue 5 mg/ml solution for injection — Summary of Product Characteristics (1 July 2024) — https://www.medicines.org.uk/emc/product/6898/smpc Dapsone 50 mg Tablets — Summary of Product Characteristics (12 June 2025) — https://www.medicines.org.uk/emc/product/100973/smpc