Toxic Alcohols
Douglas Eyolfson, MD, FRCP(C)
Department of Emergency Medicine
Health Sciences Centre
Objectives
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Review pharmacology of toxic alcohols
Review clinical presentations (suspicions)
Review evaluation strategies when
diagnosis is considered
Review immediate and definitive treatments
Introduction
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Methanol & ethylene glycol most toxic
Common ingredient
» Automotive fluids (antifreeze, windshield washer)
» De-icing solutions
» Solvents & cleaners
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Delayed Toxicity
Settings of Poisonings
Deliberate
» Suicide/homicide attempt
Non-potable intoxicant
» Indigent
» Cheap substitutes (solvents)
Inadvertent
» Amateur EtOH distilling (‘moonshine’)
» Transfer from original container (ease of pouring, found in
garages)
» Multiple poisonings
Alcohols
Ethanol
» MW = 46
» ‘0.08’ g/100ml = 18 mmol/L
» benign
Isopropyl alcohol
» Relatively benign
» Supportive care
Methanol
» MW = 32
» Toxic dose >15ml of 40%
Ethylene glycol
» MW = 62
» Toxic dose >15ml of 40%
Methanol
Parent molecule nontoxic
» Toxic metabolites
Colorless, tasteless
Toxicity > 6 mmol/L (20 mg/100ml)
Delayed toxicity (12-18h)
» Formic acid  formaldehyde
Inhibit mitochondrial respiration  lactic acidosis
Optic pappilitis & retinal edema  blindness
Ischemic injury basal ganglia
Methanol: Metabolism
Methanol: Metabolism
Rapidly absorbed
» Peak 1-2 hours
Elimination (untreated)
» Zero-order kinetics
» 2.7 mmol/L/hr
Elimination (ADH inhibition)
» 1st-order
» Pulmonary & renal
» T1/2 18-54 hours
Ethylene Glycol
Parent molecule nontoxic
Toxicity > 3 mmol/L (20 mg/100ml)
Delayed toxicity
» CNS depression, cardiovascular instability (12-24h)
Formic acid
» Nephrotoxicity (24-72h)
Glycolate
» Hypocalcemia
Oxalate acid
Ethylene Glycol: Metabolism
Ethylene Glycol: Metabolism
Rapidly absorbed
» Peak 1-2 hours
Elimination (untreated)
» 1st-order kinetics
» T1/2 3-9 hours
Elimination (ADH inhibition)
» Renal
» T1/2 3-9 hours
Evaluation
High index of suspicion
» Ingestion source unclear
» Nonpotables
» Abnormal vital signs (e.g. tachypnea in acidosis)
Labs
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Chem 10/AG/LFT’s/Osmol/ETOH/Acet/ASA
Blood gas
+ lactate
Methanol/ethylene glycol
Often delayed/unavailable
Do not wait for result before treating
Alcohols:
Anion Gap >10
» CTMUDPILES
» Consider toxic alcohols
Osmol gap
» mosmols > 10: correlate with EtOH
» If not correlating, look for toxic alcohol
» Normal range 8-12, toxic ethylene glycol >3mmol/L
» Rule in, not rule out
Treatment
ABC’s/supportive care
» IV/O2/monitor/I&O
» Immediate toxicology consult
Gastric Decontamination
» No role
Treat Acidosis
Cofactor Therapy
Antidotal therapy
Dialysis
Acidosis
Acidemia increases penetration of toxins
into cells, increasing toxicity
» Methanol  formate
» Ethylene glycol  glycolate/glyoxylate/oxalate
Treat Acidosis if pH <7.3
» 1-2 mEq/kg NaHCO3 bolus
» NaHCO3 3 amps/1L at 2 X maintenance
Cofactor Therapy
Methanol
» FormateCO2 + H2O: folate-dependant
» Folic acid 150mg IV q6h
Ethylene Glycol
» Glyoxylateglycine: pyridoxine-dependant
Pyridoxine 50mg IV
» Glyoxylateα-hydroxy-β-ketoadipate: thiamine-dependant
Thiamine 100mg IV
Give all pending specific assays
Alcohol Dehydrogenase
Inhibition
Unmetabolized methanol & ethylene glycol
nontoxic
Alcohol dehydrogenase (ADH) facilitates first
step to toxic metabolites
» Methanolformate
» Ethylene glycolglycoaldehyde
ADH inhibition inhibits progression of toxicity
EtOH
5-methylpyrazole (Fomepizole)
Ethanol
Competitive inhibitor of ADH
» ADH affinity for EtOH > methanol/ethylene glycol
Difficult to use
» Frequent measurement & titration
Sedative/behavioral effects
» Risk of aspiration
Fomepizole
Specific competitive inhibitor of ADH
Regular dosing, no titration
» 15 mg/kg load
» 10 mg/kg q12h
» Adjust dose when dialyzing
No sedation
Definitive therapy if dialysis unavailable
~$3,000.00/dose
Alternatives
IV EtOH and fomepizole unavailable
» Isolated communities
Commercial distilled spirits (40%
methanol)
» Available in most communities
» Dilute to 20%
» IV or NG
» Frequent accuchecks in children
Dialysis
Definitive therapy
» Immediate nephrology/ICU consult if OD suspected
Always with large methanol ingestions
» T1/2 18-54 hours with methanol
May be unnecessary with ethylene glycol
» T1/2 3-9 hours
Multiple Ingestions
Cluster ingestions common
» Adolescents
» Indigent
Determine if others have consumed from
same source
» May need police to apprehend patients
Preterminal Care
May present late
Irreversible neurologic damage
» Discontinuation of treatment considered
Other organs may be undamaged
» Suitable for transplant
Consider consult for organ donation
Conclusions
Delayed toxicity common
» Benign presentation
» High level of suspicion
Start treatment as soon as suspected
» Cofactors
» ADH inhibition
Call poison control/toxicologist early
Suspect multiple ingestions