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