REBEL Core Cast 90.0 – Methemoglobinemia

REBEL EM – Emergency Medicine Blog

Take Home Points

• Methemoglobinemia can result from exposure to a number of different medications. The most common are dapsone and topical anesthetic agents (i.e. benzocaine)
• Consider the diagnosis in any patient with cyanosis and hypoxia that doesn’t respond to oxygen administration
• Administer methylene blue to any patient with abnormal vital signs, metabolic acidosis, end organ dysfunction or, a serum level > 25%

REBEL Core Cast 90.0 – Methemoglobinemia

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Definition: A hemoglobinopathy characterized by an abnormal elevation of methemoglobin (MetHb) – hemoglobin in which iron (ferrous Fe²⁺) has been oxidized(ferric Fe³⁺). An abnormal MetHb level is any level > 1%.

Methemoglobinemia Pathoophysiology

Mechanism of Action

• Pathophysiology
  • Oxidized iron sites on MetHb unable to bind oxygen
  • Remaining binding sites with increased affinity for binding oxygen
  • Causes a leftward shift in the oxyhemoglobin dissociation curve
  • Results in decreased tissue oxygen delivery
• Normal situation
  • Red cells constantly exposed to oxidant stress
  • NADH MetHb reductase keeps oxidative stress in check by reducing MetHb to Fe²⁺ state
• Methemoglobinemia occurs when either
  • There is an deficiency of the reducing enzyme (NADH MetHb reductase)
  • There is increased oxidative stress that cannot be handled by the body
• Presence of MetHb renders pulse-oximetry readings inaccurate

Common Causative Agents

• Benzocaine
• Dapsone
• Nitroglycerin
• Nitrofurantoin
• Nitroprusside
• Phenazopyridine
• Sodium Nitrite
• Amyl nitrite
• Contaminated well water
• Isobutyl Nitrite (“poppers”)

Signs + Symptoms

• Low O₂ saturation that does not respond to supplemental O₂
  • Key diagnostic feature (sat < 85% w/o response to 100% FiO₂₎
  • Wavelength averaging by the pulse oximeter causes a falsely low O₂ reading
  • Since there is no true decrease in O₂ saturation, there will be no response to 100% FiO₂
• Severity of symptoms correlates closely to MetHb level and severity of impaired O₂ delivery
• Symptoms will be worse for any MetHb level in patients with baseline impairment of O₂ delivery (i.e. CHF, pneumonia, COPD, anemia)
• MetHb: < 15%
  • May be asymptomatic
  • Low pulse oximeter reading
• MetHb: 15-20%
  • Cyanosis (peripheral and central)
  • Fatigue
  • Chocolate brown colored blood
• MetHb: 20-50%
  • Dyspnea
  • Headache
  • Exercise intolerance
  • Dizziness
  • Syncope
  • Weakness
• MetHb: 50-70%
  • Tachypnea
  • Metabolic acidosis
  • Dysrhythmias
  • Seizures
  • CNS depression
  • Coma
• MetHb > 70%
  • Severe hypoxemia
  • Death

Toxicologic Assessment of Cyanosis

Management

• Source identification, removal (if possible) and decontamination
• Basic Supportive Care
  • Provide 100% FiO₂ – lack of response should raise suspicion of methemoglobinemia
  • Due to unreliability of pulse oximetry, O₂ saturation should not be sole indication for advanced airway management
• Diagnostic Testing
  • Blood gas
    • Venous blood gas (VBG) adequate
    • Arterial blood gas (AG) if obtained, will reveal a normal PaO₂
  • Co-oximeter panel for MetHb level
    • Can use a venous or arterial sample
    • Half-life 1-3 hours
• Obtain toxicology consultation (800-222-1222 in US)
• Methylene Blue
  • Mechanism of action
    • Converted to cofactor for NADPH MetHb reductase
    • Helps increase reduction of MetHb
  • Which patients should get treatment?
    • MetHb < 25% with symptoms
      • Abnormal vital signs
      • Metabolic acidosis
      • End organ dysfunction (i.e. AMS, seizures)
    • MetHb > 25% regardless of symptoms
  • Dosing
    • 1-2 mg/kg IV
    • Medication can cause local painful reaction
      • Minimize with slower infusion (over 5 minutes)
      • Flush line after infusion completed
  • Clinical improvement should occur rapidly
  • Warning: Will cause transient decrease in puse-ox level due to color of medication

Take Home Points

• Methemoglobinemia can result from exposure to a number of different medications. The most common are dapsone and topical anesthetic agents (i.e. benzocaine)
• Consider the diagnosis in any patient with cyanosis and hypoxia that doesn’t respond to oxygen administration
• Administer methylene blue to any patient with abnormal vital signs, metabolic acidosis, end organ dysfunction or, a serum level > 25%

References:

1. Price DP. Chapter 127. Methemoglobin Inducers. In: Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE. eds. Goldfrank’s Toxicologic Emergencies, 9e New York, NY: McGraw-Hill; 2011.. Link

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)

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