Methemoglobinemia

Background

• Methemoglobin refers to ferric form of hemoglobin (Fe3+) that is unable to bind O2
• Suspect in any patient with cyanosis not responsive to supplemental O2

Causes

• Rarely congenital, NADH reductase deficiency - unable to reduce ferric to ferrous iron (Fe³⁺ → Fe²⁺)
• Exposure to oxidizing agent
  • Benzocaine and other local anesthetics
  • Cyanokit, nitrites, nitrates, well water (nitrates)
  • Antimalarials
  • Quinolones
  • Dapsone (used to treat leprosy, PCP pneumonia, toxoplasmosis, dermatitis herpetiformis, brown recluse bite)
  • Aniline dyes
  • Phenazopyridine

Clinical Features

• Depends on level of metHb
  • Patients with anemia or preexisting cardiopulmonary disease will show symptoms sooner
  • <20%: asymptomatic, gray-blue cyanosis
  • 20-30%: anxiety, headache, weakness, light-headedness, tachycardia
  • 50-60%: myocardial ischemia, dysrhythmias, depressed mental status, seizure
  • >70%: usually fatal
• Ask about family or personal history of G6PD deficiency as methylene blue contraindicated

Differential Diagnosis

• Consider rare entity of sulfhemoglobinemia
  • Sulfonamides, sulfasalazine, phenazopyridine
  • Occupational exposure
  • Conventional co-oximerty misidentifies sulfhemoglobin as methemoglobin so diagnosis is suspected when patient does not respond to methylene blue
  • Typically requires no treatment other than removal of offending agent
  • Blue-green discoloration of blood

Acute dyspnea

Emergent

• Pulmonary
  • Airway obstruction
  • Anaphylaxis
  • Angioedema
  • Aspiration
  • Asthma
  • Cor pulmonale
  • Inhalation exposure
  • Noncardiogenic pulmonary edema
  • Pneumonia
  • Pneumocystis Pneumonia (PCP)
  • Pulmonary embolism
  • Pulmonary hypertension
  • Tension pneumothorax
  • Idiopathic pulmonary fibrosis acute exacerbation
  • Cystic fibrosis exacerbation
• Cardiac
  • Cardiac tamponade
  • Cardiogenic pulmonary edema (CHF)
  • Myocardial Infarction
  • Pericarditis
  • Myocarditis
• Other Associated with Normal/↑ Respiratory Effort
  • Abdominal distension
  • Anemia
  • CO Poisoning
  • Salicylate toxicity
  • Diabetic ketoacidosis (DKA)
  • Diaphragm injury
  • Electrolyte abnormalities
  • Epiglottitis
  • Flail chest
  • Hypotension
  • Metabolic acidosis
  • Pneumonia
  • Pneumothorax/hemothorax
  • Renal Failure
  • Sepsis
  • Toxic ingestion
• Other Associated with ↓ Respiratory Effort
  • Guillain-Barre syndrome
  • Multiple sclerosis
  • Myasthenia Gravis
  • Lambert-Eaton Syndrome
  • Organophosphate toxicity
  • Stroke (Main)
  • Tick paralysis

Non-Emergent

• ALS
• Ascites
• Uncorrected ASD
• Congenital heart disease
• COPD exacerbation
• Fever
• Hyperventilation
• Interstitial lung disease
• Neoplasm
• Obesity
• Panic attack
• Pleural effusion
• Polymyositis
• Porphyria
• Pregnancy
• Rib fracture
• Spontaneous pneumothorax
• Thyroid Disease
• URI

Evaluation

• Co-oximetry
  • Measures relative levels of oxyhemoglobin, carboxyhemoglobin, methemoglobin, reduced hemoglobin
  • Usually performed on arterial blood sample, but fingertip CO-oximeter devices are available
• Normal PaO2
• SpO2 will initially be falsely elevated
  • Once MetHb >30% → SpO2 will fall to 80-85%
  • Mid-80s SpO2 due to light absorption of both oxyHb and deoxyHb
• "Chocolate brown" color of blood

Management

• Methylene blue
  • Treat if symptomatic OR asymptomatic with MetHb >25%
  • 1-2mg/kg Methylene blue IV over 5min; repeat dose if no effect
  • Improvement seen within 20min
  • Contraindicated in G6PD deficiency
    • May induce acute hemolytic anemia
    • Instead use moderate dose of ascorbic acid (vitamin C), 300 to 1000 mg/day orally in divided doses
• Other treatment modalities
  • Exchange transfusion for symptomatic methemoglobinemia in patient with G6PD deficiency
  • Hyperbaric O2 when methylene blue ineffective or contraindicated
  • IV hydration and bicarbonate for metabolic acidosis

See Also

• Toxidromes
• Dyshemoglobinemia