Methemoglobinemia

Epidemiology

Etiology

Dapsone
Local/topical anesthetics (eg, benzocaine, teething medications)
Nitrates/nitrites (eg, drinking ground water)

Pathophysiology

Methemoglobin is created when reduced ferrous iron (Fe2+) bound to oxyhemoglobin is oxidized to ferric iron (Fe3+).
Ferric iron in methemoglobin cannot bind oxygen→ ↓ total blood oxygen content and ↓ blood oxygen saturation → tissue hypoxia

Tip

The ferric iron in methemoglobin has a high affinity for cyanide, thus, amyl nitrite-induced methemoglobin is used as a competitive inhibitor in the treatment of cyanide poisoning.

Clinical features

Cyanosis (brownish-blue or gray skin and membranes)

Diagnostics

Due to the wavelength of light absorbed by Fe3+ heme, pulse oximetry converges on 85% as the proportion of methemoglobin increases, regardless of the true oxygen saturation status.
Bedside testing: Blood appears dark brown (“chocolate-colored”) and does not turn red with exposure to oxygen.

Cyanide poisoning vs CO poisoning

Feature	Carbon Monoxide (CO) Poisoning	Cyanide (CN) Poisoning	Methemoglobinemia (MetHb)
Mechanism	Binds Hemoglobin (forms COHb) → ↓ O2 carrying & delivery.	Inhibits Cytochrome C Oxidase (Complex IV) → blocks ATP prod.	Iron in heme oxidized (Fe2+ → Fe3+) → cannot bind O2.
Source	Incomplete combustion (fires, car exhaust, faulty heaters).	Fires (plastics, wool), industrial, nitroprusside.	Oxidizing drugs (dapsone, nitrites, benzocaine), G6PD deficiency.
Presentation	Headache, dizziness, N/V. Cherry-red skin (late, unreliable). Normal SaO2 on pulse ox.	Rapid onset: confusion, seizures, coma. Cherry-red skin. Almond breath (unreliable).	Cyanosis (dusky/brown skin/blood) unresponsive to O2. Dyspnea.
Dx	↑ COHb level (CO-oximetry). Pulse ox misleadingly normal.	↑ Lactate. Clinical suspicion + history. High venous O2.	↑ MetHb level (co-oximetry). "Saturation gap" (pulse ox ~85%). Chocolate-brown blood.
Tx	100% O2. Hyperbaric O2 (HBO) if severe.	Hydroxycobalamin or Nitrites + Sodium Thiosulfate.	Methylene blue. O2. (Avoid MB in G6PD def.).
CT/MRI Brain	Bilateral globus pallidus lesions (hypodense CT, T2 hyper MRI).	Less specific; diffuse edema or basal ganglia lesions possible.	Non-specific hypoxic changes if severe.
O2-Myoglobin Curve	Shifts Left (impairs O2 release to muscle).	No direct significant effect.	No direct significant effect; O2-HGB curve shifts left for normal Hb.
Buzzwords	"Faulty heater," "car exhaust," "globus pallidus lesions."	"Almond breath," "plastic fire," "nitroprusside."	"Dapsone," "benzocaine," "chocolate-brown blood," "saturation gap."

Treatment

Methylene blue is the first-line treatment for acquired methemoglobinemia.
- Acts as a cofactor to reduce methemoglobin to hemoglobin

Tip

100% supplemental oxygen is not useful in methemoglobinemia, in contrast to monoxide poisoning and cyanide poisoning.