Makindo Medical Notes

Related Subjects: |Methylthioninium chloride (Methylene blue) |Methaemoglobinaemia |Drug Toxicity with Specific Antidotes

🩸 Methaemoglobinaemia — a rare but potentially life-threatening cause of hypoxia. Pulse oximetry may underestimate or overestimate oxygen saturation. Unlike normal haemoglobin, methaemoglobin (Fe³⁺) cannot release oxygen to tissues effectively → functional anaemia and hypoxia. 🚫🧠

🔎 About

• Oxidation of haem iron from ferrous (Fe²⁺) → ferric (Fe³⁺), preventing O₂ binding/release.
• Normally <1% methaemoglobin present, reduced back to Hb by methaemoglobin reductase.
• When oxidant stress overwhelms this system → hypoxia despite normal PaO₂.

⚙️ Pathophysiology

• Fe³⁺ haem groups lock Hb into a high-affinity state → O₂ can’t unload to tissues.
• Blood appears “chocolate brown” and does not turn red on exposure to air.
• Pulse oximetry becomes unreliable (may plateau ~85%).

📌 Causes

• Drugs: Dapsone, sulfonamides, phenacetin, local anaesthetics (lidocaine, benzocaine), nitrates/nitrites.
• Genetic: Cytochrome b5 reductase deficiency, Hb M variants.
• Environmental: Nitrite-contaminated water, aniline dyes, industrial chemicals.

🩺 Clinical Features

• Cyanosis not improving with O₂ therapy.
• Symptoms: breathlessness, dizziness, confusion, seizures.
• Exam: “Chocolate brown” blood, SpO₂ ~85% despite normal PaO₂.

🧪 Investigations

• ABG with co-oximetry: Gold standard → measures methaemoglobin fraction.
• Normal PaO₂ with SpO₂ ~85% is a classic clue.
• Labs: FBC, U&E, lactate (tissue hypoxia), ± metabolic acidosis.

💊 Management

• Immediate: 100% O₂ via non-rebreather; stop offending agent; ABC support.
• Methylene blue 1–2 mg/kg IV over 5 min (max 7 mg/kg/course). May repeat in 30–60 min if no response.
• Children: Same dosing (1–2 mg/kg IV, max 7 mg/kg).
• ⚠️ Contraindications:
  • G6PD deficiency → risk of haemolysis.
  • Concurrent SSRIs/SNRIs → risk of serotonin syndrome (MB is a weak MAOI).
• Resistant/severe cases → exchange transfusion or hyperbaric O₂ (specialist setting).

🚨 Key Clinical Pearls

• Always suspect in cyanosis not responding to O₂.
• Blood gas: Normal PaO₂ but patient still looks blue + chocolate-brown blood.
• Methylene blue reduces Fe³⁺ back to Fe²⁺, restoring O₂ transport — but only if NADPH pathway intact (not in G6PD deficiency).

📚 Reference

• NCBI: Methaemoglobinaemia Overview

Cases — Methaemoglobinaemia

• Case 1: A 28-year-old man attends A&E after self-treating a toothache with excessive topical benzocaine gel. He is cyanosed (lips and fingers blue) but SpO₂ reads 85% and does not improve with high-flow oxygen. Arterial blood is chocolate-brown. Methaemoglobin level: 25%. Management: High-flow O₂ continued, IV methylene blue administered (1 mg/kg over 5 minutes), and benzocaine stopped. Outcome: Within 1 hour his colour improves, SpO₂ rises >95%, and he is discharged the next day with dental review arranged.
• Case 2: A 3-year-old girl is brought in with sudden lethargy and cyanosis after drinking water from a private well. SpO₂ is persistently ~80% on O₂. Blood appears chocolate-coloured. Labs confirm methaemoglobin 35%. History reveals nitrate contamination of the well water (“blue baby syndrome”). Management: IV methylene blue given urgently, gastric protection instituted, and public health team notified to test the water supply. Outcome: Child stabilises and recovers within 24 hours. Family is advised to avoid the contaminated well and use bottled/treated water. Ongoing paediatric follow-up arranged.
• Case 3: A 39-year-old man with HIV on dapsone prophylaxis for PCP presents with gradual onset of fatigue, headache, and persistent cyanosis. SpO₂ 88% on O₂, arterial blood dark brown. Methaemoglobin level: 18%. Management: Dapsone discontinued, IV methylene blue administered, and switched to atovaquone for PCP prophylaxis. Outcome: Cyanosis improves within hours, discharged after 2 days. Haematology review confirms no underlying G6PD deficiency, so risk of recurrence is low if offending drug avoided.

Teaching Commentary 🧑‍⚕️

These three cases illustrate the main contexts of methaemoglobinaemia: 1) Acute drug-induced (benzocaine, local anaesthetics), 2) Environmental (nitrate-contaminated water, infants most at risk), 3) Chronic drug-associated (e.g. dapsone, sulphonamides). The unifying clue is cyanosis unresponsive to oxygen with chocolate-coloured blood. Treatment with IV methylene blue is highly effective but contraindicated in G6PD deficiency (risk of haemolysis). Recognition is key: misdiagnosis as asthma or pneumonia delays treatment. Outcomes are excellent with prompt therapy, but recurrent exposures must be prevented.