Rosen & Barkin's 5-Minute Emergency Medicine Consult (451 page)

BASICS

• Colorless, volatile liquid
  
• Absorbed in 30–60 min
  
• Metabolized by liver
  
• Half-life 4–8 hr
  
• Mechanism:
  
  • Inebriating
    
  • Nontoxic
    
  • Metabolites of formaldehyde and formic acid produce toxic effects.
    
  • Inhibits cytochrome oxidase.
    
• Formic acid:
  
  • Determines degree of acidosis, visual symptoms, and mortality
    
  • Directly toxic to retinal and optic nerve tissue
    
• Methanol metabolism:
  
  • Step 1: Methanol is converted to formaldehyde by liver enzyme alcohol dehydrogenase.
    
  • Step 2: Formaldehyde is then rapidly converted by aldehyde dehydrogenase to formic acid.
    
  • Step 3: Formic acid is degraded to carbon dioxide and water by folate-dependent mechanism.
    
  • Steps 1 and 3 are rate-limiting steps.
    

Common sources of methanol:

• Wood alcohol
  
• Windshield washer fluid (> 60% cases)
  
• Inhalational abuse of carburetor cleaners
  
• Fuel antifreeze solutions
  
• Formalin
  
• Gasoline
  
• Paint solvents
  
• Household cleaners
  
• Sterno cans
  
• Moonshine
  
• Model airplane fuel
  
• Photocopying fluid
  
• Perfumes
  

DIAGNOSIS

• GI:
  
  • Anorexia
    
  • Nausea/vomiting
    
  • Abdominal pain
    
• CNS:
  
  • Headache
    
  • Dizziness
    
  • Confusion
    
  • Inebriation
    
  • Coma
    
  • Seizures
    
• Ophthalmologic:
  
  • Blurry/hazy vision
    
  • Photophobia
    
  • “Snowfield vision”
    
  • Blindness
    
  • Central scotoma
    

• Intentional or unintentional methanol ingestion
  
• No history, but a patient with an unexplained high anion gap metabolic acidosis
  
• Elevated unexplained osmol gap
  

• Optic disc:
  
  • Hyperemia or pallor
    
  • Papilledema
    
• Afferent pupillary defect
  
• Tachypnea
  
• Altered mental status
  

• History of all substances ingested
  
• Inquire about visual symptoms.
  
• Funduscopic exam
  
• Drawn simultaneously:
  
  • Arterial blood gas
    
  • Serum methanol, ethylene glycol, isopropyl alcohol, and ethanol levels
    
  • Electrolytes, BUN, creatinine, and glucose
    
  • Measured serum osmolality (by freezing-point depression is preferred)
    

• Calculate anion gap = (Na
  ⁺
  ) – (Cl
  ⁻
  + HCO
  ₃
  ⁻
  ):
  
  • Normal = 8–12.
    
• Determine serum osmol gap:
  
  • Osmol gap = measured osmolality – calculated osmolarity:
    
  • Calculated osmolarity = 2(Na
    ⁺
    ) + glucose/18 + BUN/2.8 + ethanol (in mg/dL)/4.6.
    
• Osmol gap:
  
  • Screens for methanol (methanol is osmotically active, toxic metabolites are not)
    
  • Most sensitive early in poisoning and normalizes as methanol is metabolized or with concurrent ethanol ingestion
    
  • Traditionally an osmol gap >10 is considered indication for ruling out occult methanol ingestion. However, potentially toxic serum concentrations of methanol can be present with osmol gap <10.
    
  • A negative osmol gap DOES NOT rule out a methanol exposure.
    
  • Ethanol has higher affinity for alcohol dehydrogenase than methanol. With concurrent ethanol ingestion, osmol gap tends to be larger and acidosis tends to be less severe because relatively less methanol has been converted to acid-producing metabolites.
    
• Serum methanol concentrations
  confirm
  methanol poisoning:
  
  • Late after ingestion, no parent compound (methanol) may be detected and severe high anion gap metabolic acidosis will be present.
    
• Ethanol concentration may have clinical implications and is pertinent in interpreting lab tests.
  

CT brain

• Increased osmol gap:
  
• ME DIE A
  :
  
  • M
    ethanol
    
  • E
    thanol
    
  • D
    iuretics/diluents (mannitol, glycerin, sorbitol, propylene glycol)
    
  • I
    sopropyl alcohol
    
  • E
    thylene glycol
    
  • A
    cetone, ammonia
    
• Elevated anion gap metabolic acidosis:
  A CAT MUDPILES
  :
  
  • A
    lcoholic ketoacidosis
    
  • C
    yanide, CO, H
    ₂
    S, others
    
  • A
    cetaminophen
    
  • A
    ntiretrovirals (NRTI)
    
  • T
    oluene
    
  • M
    ethanol, metformin
    
  • U
    remia
    
  • D
    iabetic ketoacidosis
    
  • P
    araldehyde, phenformin, propylene glycol
    
  • I
    ron, INH
    
  • L
    actic acidosis
    
  • E
    thylene glycol
    
  • S
    alicylate, acetylsalicylic acid (ASA; aspirin), starvation ketosis
    

TREATMENT

• Transport all possibly ingested substances.
  
• Dermal decontamination of a methanol spill by clothing removal, irrigation with soap and water
  
• Monitor airway and CNS depression.
  

• Airway, breathing, and circulation (ABCs)
  
• Dextrose, naloxone, and thiamine for altered mental status
  
• Prevent further methanol absorption:
  
  • Gastric lavage with nasogastric tube:
    
    • Likely not helpful because of rapid absorption of methanol and delay in presentation >1 hr
      
  • Activated charcoal:
    
    • For potential coingestants
      
    • Poorly adsorbs methanol
      
    • Aspiration risk for patients with altered mental status
      

• Prevent methanol conversion to toxic metabolites with fomepizole (preferable) or ethanol infusion
  
• Fomepizole (4-MP, Antizol):
  
  • Competitive inhibitor of alcohol dehydrogenase
    
  • Indications:
    
    • Intentional methanol ingestion
      
    • Accidental methanol ingestion of more than a sip
      
    • Altered mental status or visual symptoms associated with unexplained osmol gap and/or elevated anion gap metabolic acidosis
      
  • Initiate before serum methanol level returns if intentional ingestion or more than a sip.
    
  • Continue until methanol level is <25 mg/dL.
    
  • Advantages:
    
    • No need for continuous infusion
      
    • No inebriation/CNS depression
      
    • Ease of dosing
      
    • No hypoglycemia, no hyponatremia, no hyperosmolality
      
    • No checking serum concentrations
      
    • Reduced nursing care and monitoring
      
    • Occult methanol exposure can often be ruled out before 2nd dose is needed.
      
  • Disadvantages:
    
    • Blurry vision
      
    • Transient elevation of liver function tests
      
• Ethanol therapy:
  
  • Not FDA approved for treatment of methanol
    
  • Ethanol has greater affinity than methanol for alcohol dehydrogenase:
    
    • Slows metabolism to formaldehyde and formic acid by competitive inhibition
      
  • Ethanol is the 2nd-choice antidote if fomepizole is not available.
    
  • Initiate before methanol level returns if potentially toxic ingestion is highly suspected or confirmed by history:
    
    • Therapeutic range is 100 mg/dL.
      
  • Continue until methanol level is <25 mg/dL.
    
  • Indications for ethanol therapy:
    
    • Intentional methanol ingestion
      
    • Accidental methanol ingestion of more than a sip
      
    • Altered mental status or visual symptoms associated with unexplained osmol gap and or elevated anion gap metabolic acidosis
      
  • Advantages:
    
    • Easily accessible
      
    • Oral and IV routes
      
  • Disadvantages:
    
    • CNS depression especially in children
      
    • Respiratory depression
      
    • Hyponatremia or hypernatremia
      
    • Hypoglycemia
      
    • Hyperosmolarity
      
    • Continuous infusion
      
    • Frequent lab testing
      
    • Contraindicated in pregnancy
      
    • Pancreatitis
      
    • Gastritis
      
• Enhance elimination of methanol and toxic metabolites with hemodialysis:
  
  • Decreases elimination half-life of methanol
    
  • Removes formaldehyde and formic acid
    
  • Indications:
    
    • Ingestion of >1 mL/kg of 100% methanol
      
    • Ophthalmologic manifestations
      
    • Severe metabolic acidosis unresponsive to bicarbonate therapy
      
    • Persistent electrolyte or metabolic acidosis
      
    • Renal insufficiency
      
    • Serum methanol level >25 mg/dL
      
  • Continue hemodialysis until methanol level approaches <25 mg/dL and the metabolic acidosis has resolved.
    
• Folic acid and folinic acid (leucovorin):
  
  • Folic acid: Cofactor required for conversion of formic acid to carbon dioxide and water
    
  • Supplemental folate important in malnourished individuals (alcoholics)
    
• Correct acid–base abnormalities:
  
  • Sodium bicarbonate for severe acidosis (pH <7.1)
    
  • The goal of the sodium bicarbonate drip is to maintain a normal serum pH.