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
| Level | Typical findings |
|---|
| <1% | Normal |
| 3–5% | Minor skin discoloration |
| 15–20% | Cyanosis ± no symptoms |
| 25–50% | Dyspnoea, headache, anxiety, confusion |
| >50% | Severe hypoxia, seizures, arrhythmia, coma |
- 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
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.
