Toxic AlcoholsRama B. Rao

Bellevue/NYU Medical Center

New York City Poison Control Center

Alcohols: R-OH

H-C-OH

H

H

Methanol1C

H-C-OH

H

H-C-OH

H

Ethylene Glycol2C

H-C-H

H

H-C-H

OH

Ethanol2C

H-C-H

H

H-C-OH

H-C-H

H

H-C-H

H

H-C-OH

H-C-OH

H

Isopropanol3C

Propylene Glycol3C

H-C-OH

H

Benzyl Alcohol

Alcohols: R-OH

Ethanol

H-C-H

H

H-C-H

OH

Ethanol

H-C-H

H

C-H

O

H-C-H

H

C-OH

O

Acetaldehyde Acetic Acid

ADH ALDH

ADH = Alcohol DehydrogenaseALDH = Aldehyde Dehydrogenase

Methanol

• Molecular weight 32

• Low freezing point

• Highly volatility

H-C-OH

H

H

Methanol

Methanol

• Gas Line Antifreeze 100%

• Windshield washer fluid 30%

• Varnish removers• Fuel for food

warming 3-70%• Industrial uses

Methanol Metabolism

H-C-OH

H

H

Methanol

H-C-OH

H

O

Formaldehyde

H-C-H

H

O

Formic Acid

ADH ALDH

ADH: Alcohol DehydrogenaseALDH: Aldehyde Dehydrogenase

Methanol Toxicity

• Delayed onset (8-12hrs)

• Anion gap acidosis– Tachypnea– Visual complaints

• Retinal metabolism

• “Snow storm”Yang CS et al Eye 2005;19:806-809

Methanol Toxicity

• CNS depression– Bilateral hemmorhage

putamen

• Abdominal pain

• Multisystem organ failure

University of Western Ontario:Neurology Collection

Ethylene Glycol

• Molecular Weight 62

• Low Volatility

• High boiling point

H-C-OH

H

H-C-OH

H

Ethylene Glycol

Ethylene Glycol

• Coolant/Antifreeze

• Solvents

• De-Icer

Ethylene Glycol Metabolism

H-C-OH

H

H-C-OH

H

Ethylene Glycol

H-C-OH

H

C-H

O

H-C-OH

H

C-OH

O

Glycoaldehyde Glycolic Acid

ADH ALDH

ADH = Alcohol dehydrogenaseALDH = Aldehyde dehydrogenase

Ethylene Glycol Metabolism

H-C-OH

H

C-OH

O

Glycolic Acid

H-C-H

O

C-OH

O

H-C-OH

O

C-OH

O

Glyoxylic Acid Oxalic Acid

LDH

LDH = Lactate dehydrogenase

-OH- Ketoadipic Acid Glycine + Benzoic Acid

Hippuric Acid

B1, Mg2+ B6

Ethylene Glycol Toxicity

• Onset 4-6 hours

• Anion gap acidosis

• Tachypnea 

    

pH

Ethylene Glycol Toxicity

• Abdominal pain

• Hypocalcemia

• Calcium oxalate crystals in urine

• Renal failure

Identifying Patients for Treatment: Methanol/EG

• Serum ethylene glycol or methanol level

• Action level for treatment: 25 mg/dL*

* Or any level with acidosis

Treatment• Limit absorption:• Prevent metabolism or parent

compound to toxic metabolite

• Enhance elimination – Parent– Metabolites

• Correct Derangements

NG Tube

ADH Inhibition

Substrates/Other

Hemodialysis

Limits of Serum Levels

• Useful prior to onset of acidosis or in massive overdoses

• Parent compound not directly toxic

• Levels not universally available

Time

EG or Methanol

Anion Gap

Arterial Blood Gas/Lactate

• Acidosis indicates advanced poisoning

• Lactate usually low*

• Patients with acidosis should receive treatment

*Some glycolates are misidentified as lactate

• Serum ethanol inhibits metabolism of EG and Methanol

• Onset of toxicity EG/Methanol may be delayed

Adjunctive Information:Ethanol

Adjunctive Information: Osmol Gap

• Osmol Gap = Measured-Calculated Osmols

• Calculated:2 Na + BUN + Glucose + Alcohol

• N = MW Alcohol/10• Must use freezing point depression

2.8 18 N

Osmol Gap: Limitations• Normal Osmol gap in

between – 14 ± 10

• Normal Osmol Gap in setting of poisoning does not rule out a treatable level

• Osmol Gap diminishes as parent compound is metabolized

Time

Osmol Gap

Anion Gap

Adjunctive Information

• Ethylene glycol:– Limited utility of

fluorescence of urine– May note crystals in urine

• Methanol– Hyperemia retina or visual

complaints

Treatment: Methanol or Ethylene Glycol

• Level 25 mg/dL or

• Anion gap metabolic acidosis ( non-lactate) with strong suspicion EG or Methanol exposure

• Ethanol more avid for ADH– 6-8x more avid than ethylene glycol– 4x more avid than methanol

Aldehyde AcidADH ALDHMethanol

Ethanol

Ethylene Glycol

Treatment

Ethanol

• Concentration = Dose

• Vd of ethanol = 0.6 L/kg

• Desired concentration 100-200 mg/dL

Vd (wt in kg)

Ethanol

• Target concentration 100 mg/dL

• Proof is 2x concentration– 80 proof is 40% ethanol or 40 grams/100 mL

• 0.8 gm/kg loading IV of 10% solution over 1 hour = 8 mL/kg of 10% solution

Ethanol Infusion

• 80-130 mg/kg/hour depending on how fast a patient metabolizes

• Needs to be increased to 250 mg/kg/hour or higher during dialysis

Ethanol Infusion: Management

• Serial ethanol levels

• Watch glucose* and sodium*

• Observe for respiratory status*

* Especially in children

Fomepizole

• A blocker of alcohol dehydrogenase

• Has replaced ethanol as the agent of choice in known or suspected exposures

• Minimal adverse effects

Hemodialysis

• Consult nephrology early in acidemic patients

• Levels toxic alcohol 25 mg/dL

Adjuncts for Methanol Poisoning

• Sodium bicarbonate– pH < 7.30

– Can ion trap formic acid in urine and enhance elimination

• Folate administration– Facilitates conversion of one carbon fragments to CO2

– 1mg/kg up to 50 mg every 4 hours

Adjuncts for Ethylene Glycol Poisoning

H-C-OH

H

C-OH

O

Glycolic Acid

H-C-H

O

C-OH

O

H-C-OH

O

C-OH

O

Glyoxylic Acid Oxalic Acid

LDH

LDH = Lactate dehydrogenase

-OH- Ketoadipic Acid Glycine + Benzoic Acid

Hippuric Acid

B1, Mg2+ B6

• To enhance metabolism away from oxalates*– Thiamine 100 mg every 4- 6 hours– Pyridoxine 50 mg every 4-6 hours

Adjuncts for Ethylene Glycol Poisoning

* Limited data

Diethylene Glycol

• Elixir of Sulfanilamide disaster 1937-38

• Renal failure 105 deaths

• U.S. Legislation of Drug Safety

Benzyl Alcohol

• Preservative in some medications

• Gasping Baby Syndrome– Potentially fatal in

neonates

H-C-OH

H

Benzyl Alcohol

Isopropanol

• Metabolized to acetone

• No acidosis

• Supportive care

H-C-H

H

H-C-OH

H-C-H

H

Isopropanol3C

Glycol Ethers

• Brake fluid

• Solvents

• Rarely metabolized to ethylene glycol

• Supportive care

Propylene Glycol

• Metabolized to lactate

• Acidosis in ingestion

• IV as diluent QRS widening, hypotension*

H-C-H

H

H-C-OH

H-C-OH

H

Propylene Glycol

* Phenytoin diluent

Summary

• For Methanol/EG Poisoning– Early Level, ABG, Lactate, Ethanol level– Caution in using osmol gap – Antidote: Ethanol or Fomepizole ( not both)– Hemodiaylsis– Consider sodium bicarbonate/folate for

methanol– Thiamine and Pyridoxine for EG