Rosen & Barkin's 5-Minute Emergency Medicine Consult (452 page)

• Activated charcoal: 1 g/kg PO
  
• Dextrose: D
  ₅₀
  W 1 amp: 50 mL or 25 g (peds: D
  ₂₅
  W 2–4 mL/kg) IV
  
• Fomepizole:
  
  • Loading dose: 15 mg/kg slow infusion over 30 min
    
  • Maintenance dose: 10 mg/kg q12h for 4 doses, then 15 mg/kg q12h until methanol levels reduced <25 mg/dL
    
  • Dosing related to hemodialysis:
    
    • Do not administer dose at beginning of dialysis if last dose was <6 hr previously.
      
    • Administer next dose if last dose was >6 hr previously.
      
    • Dose q4h during dialysis.
      
    • If time between last dose and end of dialysis was <1 hr from last dose, do not administer new dose.
      
    • If time between last dose and end of dialysis was 1–3 hr from last dose, administer 1/2 of next scheduled dose.
      
    • If time between last dose and end of dialysis was >3 hr from last dose, administer next scheduled dose.
      
• Ethanol:
  
  • Oral: 50% ethanol solution (100-proof liquor) via nasogastric tube:
    
    • Loading dose 2 mL/kg
      
    • Maintenance dose 0.5 mL/kg/h
      
    • Maintenance dose during hemodialysis 1 mL/kg/h
      
  • IV: 10% ethanol in D
    ₅
    W:
    
    • Loading dose 8 mL/kg over 30–60 min
      
    • Maintenance infusion 2 mL/kg/h
      
    • Maintenance infusion during hemodialysis 4 mL/kg/h
      
• Folic acid: 50 mg IV q4h for 24 hr
  
• Sodium bicarbonate: 1–2 mEq/kg in 1 L of D
  ₅
  W with 40 mEq KCl at 250 mL/h
  

FOLLOW-UP

• Significant historical methanol ingestion even if initially asymptomatic
  
• ICU admission for seriously ill patients
  
• Transfer to another facility if hemodialysis or antidote is indicated but not readily available.
  

Asymptomatic patient with isolated methanol ingestion if serum methanol level is <25 mg/dL; normal acid/base status and electrolytes.

Psychiatric follow-up for suicidal/depressed patients

• An osmol gap <10 mmol/L does not rule out a methanol exposure.
  
• If you have a patient with an elevated anion gap and methanol exposure is in the differential diagnosis, administer fomepizole immediately and confirm exposure with a serum concentration.
  
• If you cannot confirm a methanol exposure, or do not have hemodialysis capabilities 24/7, or have no antidote, transfer the patient to a facility that has all of these capabilities.
  
• Not all patients will have an elevated osmol and anion gap. Early presenters will have an osmol gap only, because methanol is osmotically active, and there are no toxic metabolites yet. Late presenters may have an anion gap only, because the osmotically active parent compound has metabolized to the toxic acidotic metabolites. Patients who present in between will have a combination of an anion gap and an osmol gap.
  

• Desai T, Sudhalkar A, Vyas U, et al. Methanol poisoning predictors of visual outcomes.
  JAMA Ophthalmol.
  2013;131(3):358–364.
  
• Leikin J, Paloucek F. Fomepizole.
  Leikin and Paloucek’s Poisoning and Toxicology Handbook.
  4th ed. New York, NY: Lexi-Comp; 2008:989.
  

CODES

980.1 Toxic effect of methyl alcohol

BASICS

• Iron molecule in hemoglobin is oxidized from ferrous (Fe
  ²⁺
  ) to ferric (Fe
  ³⁺
  ) state resulting in a form of hemoglobin that cannot transport oxygen.
  
• Oxygen-carrying capacity of blood is reduced and cyanosis is generally present with significant levels.
  
• Normal methemoglobin levels are ≤1%; symptoms usually occur with levels >20%.
  
• More serious with coexisting anemia
  
• Methemoglobin:
  
  • Decreases total oxygen-carrying capacity (functional anemia)
    
  • Shifts hemoglobin oxygen-dissociation curve to the left, impairing O
    ₂
    release to tissues
    
  • Maintained at physiologic level (1–2%) by nicotinamide adenine dinucleotide (NADH)-methemoglobin (cytochrome B
    ₅
    ) reductase in red blood cells (RBCs)
    
• Congenital methemoglobinemia:
  
  • NADH-methemoglobin (cytochrome B
    ₅
    ) reductase deficiency (homozygous or heterozygous)
    
  • Heterozygous hemoglobin M and other abnormal hemoglobins
    
• Acquired methemoglobinemia results from oxidant stress on RBCs:
  
  • Some methemoglobin-inducing agents are direct oxidants (e.g., nitrites)
    
  • Many substances produce oxidant injury via
    N
    -hydroxylamine metabolites.
    
  • Methemoglobinemia may be delayed relative to initial substance exposure.
    
• Many methemoglobin-inducing agents also cause Heinz body hemolytic anemia (HA):
  
  • Caused by oxidant injury of RBC proteins
    
  • Glucose-6-phosphate dehydrogenase (G6PD)–deficient patients have higher risk.
    
  • Patients with methemoglobinemia should be worked up for HA.
    
• Methemoglobinemia may serve as marker for genetic abnormalities:
  
  • Heterozygous NADH-methemoglobin (cytochrome B
    ₅
    ) reductase deficiency
    

• Cyanide (CN) antidote kit:
  
  • Induces methemoglobinemia via amyl and sodium nitrite
    
  • CN will preferentially complex with methemoglobin, which can then be chelated by sodium thiosulfate.
    
• Nitrates/nitrites:
  
  • Nitrites (NO
    ₂
    )
    
  • Nitrates (NO
    ₃
    ) (e.g., nitroglycerine, via metabolic conversion to nitrites)
    
  • Nitric oxide (NO)
    
• Dyes:
  
  • Aniline dyes
    
  • Methylene blue (excessive)
    
• Antiparasitic drugs (high potential for MetHb formation):
  
  • Dapsone
    
  • Primaquine
    
  • Chloroquine
    
• Local anesthetics (high potential for MetHb formation):
  
  • Benzocaine
    
  • Lidocaine
    
  • Prilocaine
    
• Analgesics:
  
  • Phenazopyridine (Pyridium)
    
  • Phenacetin
    
• Antibiotics:
  
  • Nitrofurantoin
    
  • Sulfones
    
  • Sulfonamides
    
• Others:
  
  • Metoclopramide
    
  • Naphthalene (mothballs)
    
  • Paraquat (herbicide)
    
  • Arsine gas (AsH
    ₃
    )
    
  • Chlorates (ClO
    ₄
    )
    
  • Phenols (e.g., dinitrophenol, hydroquinone)
    

DIAGNOSIS

• Central cyanosis, refractory to oxygen administration:
  
  • Cyanosis evident at methemoglobin (MetHb) of 10–15% of total hemoglobin in nonanemic patient (or 1.5 g of MetHb/dL blood)
    
• Dyspnea/tachypnea
  
• Chest pain/dysrhythmias
  
• Syncope
  
• Altered mental status with levels >50%
  

• Exposure to methemoglobin-inducing agent
  
• All substances ingested and time(s) of ingestion
  
• G6PD deficiency
  
• Medical conditions vulnerable to impaired oxygen delivery (e.g., coronary artery disease)
  

• Cyanosis
  
• Emphasis on mental status and cardiovascular findings
  
• Icterus or dark-colored urine with accompanying HA
  

• Pulse oximetry is
  inaccurate
  in methemoglobinemia:
  
  • MetHb interferes with pulse oximetry measurement of hemoglobin oxygen saturation.
    
  • Saturation decreases to ∼85% with increasingly more severe methemoglobinemia.
    
  • Pulse oximetry cannot be used to guide management.
    
• ABG for:
  
  • Methemoglobin level
    
  • Carboxyhemoglobin level
    
  • PaO
    ₂
    and PaCO
    ₂
    
• ECG
  

• Blood classically described as chocolate colored
  
• CBC with manual differential count and smear analysis for evidence of HA
  

CXR to rule out other pulmonary pathology

• Hypoxia:
  
  • CHF
    
  • COPD
    
  • Pulmonary embolism
    
• Irritant gas exposure
  
• Blue discoloration:
  
  • Hypoxia
    
  • Sulfhemoglobinemia
    
  • CN poisoning
    
  • Hydrogen sulfide poisoning
    
  • Excess methylene blue administration
    
  • Tellurium toxicity
    
  • Skin contact/staining with blue dye