Kim – Toxic Hemoglobinopathies

Dr. Hong Kim is back – this time to discuss two classic hemoglobinopathies. Do you you know the common iatragenic causes of methemoglobinemia?  How about when to send a patient for hyperbaric oxygen for carbon monoxide exposure?  If not, this is a can’t miss lecture.

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Written summary by Ahmad Aswad

Carbon Monoxide Toxicity

• In the U.S. common sources of exposure include residential fire (with cyanide as a potential co-exposure), engine exhaust, natural gas appliances, propane-powered engines, & paint stripper ingestion.
• Normal: Physiologic carboxyhemoglobin (COHb) levels: 1-2% in healthy individuals, up to 5-10% in smokers!
• Pathophysiology: Once inhaled/absorbed it binds to hemoglobin with 250 times higher affinity than oxygen causing “functional” anemia. Mitochondrial dysfunction also a major cause of clinical decompensation.
• Symptoms: At about 10%: Begins with headache, dizziness at level >10%, can progress to unconsciousness, death with levels above 50%
• Diagnosis
  • Lab: CO-oximetry
  • Radiology: CT head shows basal ganglia lesions
• Treatment
  • Primary treatment: Removal from exposure, 100% FiO₂ by non-rebreather mask
  • t_1/2: CO half-life is 5 hours
  • Hyperbaric Oxygen (HBO) Therapy: causes dissociation of CO from Hb, myoglobin, and cytochrome oxidase in the mitochondria
    • Decreases half-life to 23 minutes
    • HBO may also antagonize lipid peroxidation and decrease leukocyte adhesion, minimizing the inflammatory response.
    • Survivors may develop delayed neuropsychiatric sequelae and cognitive impairment weeks after exposure.
    • Risk factors of delayed reactions include LOC, age> 30 & duration of CO exposure.
    • Case reports suggest that HBO initiated within 6 hours from exposure may prevent delayed neurologic sequelae
    • Indications for HBO
      • Levels of CO Hb >25 %, ( >15 % in pregnant and pediatric population, expert opinion)
      • Clinical symptoms: Chest pain, dizziness, syncope, seizures, coma, focal neurological findings, pregnancy
      • Cochrane review: insufficient evidence to support HBO use
      • American college of emergency physicians (ACEP): HBO a therapeutic option, cannot be mandated

Methemoglobin (MetHb)

• Both hereditary & toxic forms of methemoglobinemia exist
• Normal levels are 1-3%
• Pathophysiology: Oxidizes iron moiety to Fe³⁺ in hemoglobin leading to inability to carry oxygen.
• Clinical findings
  • May not be symptomatic up until levels above 20%, with death occurring at levels above 70%
  • Pulse oximetry shows hypoxemia with saturation levels <90%
  • SpO2 usually stays around 85% as levels of MetHb increase
• Precipitants
  • Common drugs: Dapsone, benzocaine, phenazopyridine, amyl nitrites and anti-malarials.
  • Chemicals such as aniline dye, organic nitrites, and nitrates food preservatives.
• Treatment: Methylene blue
  • Indication: Symptomatic patients and MetHb >25%. Response is seen within minutes and dose may be repeated once.
  • Mechanism: Fe³⁺ oxidized to Fe²⁺ via NADPH dependent pathway
  • Can cause hemolysis, decreased pulse-oximetry, and can potentially cause serotonin syndrome.
  • Can be considered in patients with G6PD deficiency only in very life threatening cases, as hemolysis will often be seen 24 hours later.
  • Alternative treatment options: Exchange transfusion, HBO, and ascorbic acid (slow response)