methemoglobinaemia

pathophysiology

• Oxidation: Iron in Haemoglobin (Hb) is oxidized from Ferrous ($F{e}^{2+}$) to Ferric ($F{e}^{3+}$) by an oxidizing agent.
• Consequences:
  1. $F{e}^{3+}$ cannot carry Oxygen.
  2. Remaining normal heme sites have increased affinity for $O_2$ (Left shift of dissociation curve).
  3. Result: Functional anemia + Tissue Hypoxia.

causes

• Drugs (Oxidizing Agents):
  • Local Anaesthetics: Benzocaine, Lidocaine, Prilocaine (EMLA).
  • Antibiotics: Dapsone, Sulfonamides (Septra/Bactrim), Chloroquine.
  • Nitrates: Nitroglycerin, Nitroprusside, Nitric Oxide, Amyl Nitrite (“Poppers”).
• Genetic:
  • G6PD Deficiency (Predisposes to oxidant stress).
  • NADH Methemoglobin Reductase Deficiency.
  • Hemoglobin M disease.
• Other: Well water (infants - nitrates).

clinical presentation

Symptoms correlate with MetHb Level:

• 3–15%: Asymptomatic or slate-grey skin discolouration. SpO2 reads 90–95%.
• 15–20%: Cyanosis (“Chocolate Brown Blood”). SpO2 ~85%.
• 20–50%: Headache, fatigue, dizziness, syncope, dyspnea, weakness.
• > 50%: CNS depression, seizures, coma, metabolic acidosis, arrhythmias.
• > 70%: Usually fatal.

diagnosis

• The “Saturation Gap”:
  • Pulse Oximetry (SpO2): Reads falsely low (typically plateaus at 85% regardless of true saturation) because MetHb absorbs light at both 660nm and 940nm.
  • Arterial Blood Gas (PaO2): Normal (or high if on supplemental $O_2$), because dissolved oxygen is unaffected.
  • Result: Clinical Cyanosis + “Low” SpO2 + Normal PaO2.
• Co-Oximetry: The gold standard. Measures percentage of MetHb directly.
• Bedside Test: Blood looks dark “chocolate brown” and does not brighten when shaken with air (oxygen).

management

1. supportive

• Stop offending agent.
• 100% Oxygen: (To saturate any remaining normal Hb).
• Coma/Seizures: Intubate and supportive care.

2. antidote: methylene blue

• Indication: Symptomatic (e.g., dyspnea, chest pain, altered mental status) OR MetHb > 30%.
• Dose: 1–2 mg/kg IV over 5 minutes.
  • Repeat: Can repeat in 30–60 mins if no response.
• Mechanism: Accelerates reduction of MetHb back to Hb via NADPH pathway.
• Contraindications:
  • G6PD Deficiency: Methylene blue requires G6PD to work; can cause severe hemolysis in deficient patients.
  • Serotonin Syndrome Risk: Methylene blue is an MAOI. Caution with SSRIs.

3. alternatives

• Ascorbic Acid (Vitamin C): Theoretical benefit (slow reducing agent). Used if Methylene Blue is contraindicated or unavailable.
• Exchange Transfusion: For severe, life-threatening cases (or severe G6PD deficiency).
• Cimetidine: Specifically inhibits dapsone metabolism (preventing further oxidant production).