Toxic Alcohols
Douglas Eyolfson, MD, FRCP(C)Department of Emergency Medicine
Health Sciences Centre
Objectives
Review pharmacology of toxic alcohols Review clinical presentations (suspicions) Review evaluation strategies when
diagnosis is considered Review immediate and definitive treatments
Introduction
Methanol & ethylene glycol most toxic Common ingredient
» Automotive fluids (antifreeze, windshield washer)» De-icing solutions» Solvents & cleaners
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» 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
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» FormateCO2 + H2O: folate-dependant» Folic acid 150mg IV q6h
Ethylene Glycol» Glyoxylateglycine: pyridoxine-dependant
Pyridoxine 50mg IV» Glyoxylateα-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» Methanolformate» Ethylene glycolglycoaldehyde
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
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