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Toxic Alcohols. Rama B. Rao Bellevue/NYU Medical Center New York City Poison Control Center. Alcohols: R- OH. OH. H. H. H-C - H. H-C -OH. H-C -OH. H-C - H. H-C -OH. H. H. H. Methanol 1C. Ethanol 2C. Ethylene Glycol 2C. Alcohols: R- OH. H. H. H. H-C - H. H-C -OH. H-C -OH.

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toxic alcohols

Toxic Alcohols

Rama B. Rao

Bellevue/NYU Medical Center

New York City Poison Control Center

alcohols r oh
Alcohols: R-OH

OH

H

H

H-C-H

H-C-OH

H-C-OH

H-C-H

H-C-OH

H

H

H

Methanol

1C

Ethanol

2C

Ethylene Glycol

2C

slide3

Alcohols: R-OH

H

H

H

H-C-H

H-C-OH

H-C-OH

H-C-OH

H-C-OH

H-C-H

H-C-H

H

H

Benzyl Alcohol

Isopropanol

3C

Propylene Glycol

3C

ethanol
Ethanol

OH

O

O

H-C-H

C-H

C-OH

ADH

ALDH

H-C-H

H-C-H

H-C-H

H

H

H

Ethanol

Acetaldehyde

Acetic Acid

ADH = Alcohol Dehydrogenase

ALDH = Aldehyde Dehydrogenase

methanol
Methanol
  • Molecular weight 32
  • Low freezing point
  • Highly volatility

H

H-C-OH

H

Methanol

methanol6
Methanol
  • Gas Line Antifreeze 100%
  • Windshield washer fluid 30%
  • Varnish removers
  • Fuel for food warming 3-70%
  • Industrial uses
methanol metabolism
Methanol Metabolism

H

O

O

ADH

ALDH

H-C-OH

H-C-H

H-C-OH

H

H

H

Methanol

Formaldehyde

Formic Acid

ADH: Alcohol Dehydrogenase

ALDH: Aldehyde Dehydrogenase

methanol toxicity
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 toxicity9
Methanol Toxicity
  • CNS depression
    • Bilateral hemmorhage putamen
  • Abdominal pain
  • Multisystem organ failure

University of Western Ontario:

Neurology Collection

ethylene glycol
Ethylene Glycol
  • Molecular Weight 62
  • Low Volatility
  • High boiling point

H

H-C-OH

H-C-OH

H

Ethylene Glycol

ethylene glycol12
Ethylene Glycol
  • Coolant/Antifreeze
  • Solvents
  • De-Icer
ethylene glycol metabolism
Ethylene Glycol Metabolism

H

O

O

H-C-OH

C-H

C-OH

ADH

ALDH

H-C-OH

H-C-OH

H-C-OH

H

H

H

Ethylene Glycol

Glycoaldehyde

Glycolic Acid

ADH = Alcohol dehydrogenase

ALDH = Aldehyde dehydrogenase

ethylene glycol metabolism14
Ethylene Glycol Metabolism

O

O

O

C-OH

C-OH

C-OH

LDH

H-C-OH

H-C-H

H-C-OH

H

O

O

Glyoxylic Acid

Glycolic Acid

Oxalic Acid

B1, Mg2+ B6

-OH- Ketoadipic Acid Glycine + Benzoic Acid

Hippuric Acid

LDH = Lactate dehydrogenase

ethylene glycol toxicity
Ethylene Glycol Toxicity
  • Onset 4-6 hours
  • Anion gap acidosis
  • Tachypnea

pH

ethylene glycol toxicity16
Ethylene Glycol Toxicity
  • Abdominal pain
  • Hypocalcemia
  • Calcium oxalate crystals in urine
  • Renal failure
identifying patients for treatment methanol eg
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
Treatment

NG Tube

  • Limit absorption:
  • Prevent metabolism or parent compound to toxic metabolite
  • Enhance elimination
    • Parent
    • Metabolites
  • Correct Derangements

ADH Inhibition

Substrates/Other

Hemodialysis

limits of serum levels
Limits of Serum Levels
  • Useful prior to onset of acidosis or in massive overdoses
  • Parent compound not directly toxic
  • Levels not universally available

EG or Methanol

Anion Gap

Time

arterial blood gas lactate
Arterial Blood Gas/Lactate
  • Acidosis indicates advanced poisoning
  • Lactate usually low*
  • Patients with acidosis should receive treatment

*Some glycolates are misidentified as lactate

adjunctive information ethanol
Adjunctive Information:Ethanol
  • Serum ethanol inhibits metabolism of EG and Methanol
  • Onset of toxicity EG/Methanol may be delayed
adjunctive information osmol gap
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
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

Osmol Gap

Anion Gap

Time

adjunctive information
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
Treatment: Methanol or Ethylene Glycol
  • Level  25 mg/dL or
  • Anion gap metabolic acidosis ( non-lactate) with strong suspicion EG or Methanol exposure
slide26

Treatment

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

Methanol

Ethanol

Ethylene Glycol

ADH

ALDH

Aldehyde

Acid

ethanol27
Ethanol
  • Concentration = Dose
  • Vd of ethanol = 0.6 L/kg
  • Desired concentration 100-200 mg/dL

Vd (wt in kg)

ethanol28
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
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
Ethanol Infusion: Management
  • Serial ethanol levels
  • Watch glucose* and sodium*
  • Observe for respiratory status*

* Especially in children

fomepizole
Fomepizole
  • A blocker of alcohol dehydrogenase
  • Has replaced ethanol as the agent of choice in known or suspected exposures
  • Minimal adverse effects
hemodialysis
Hemodialysis
  • Consult nephrology early in acidemic patients
  • Levels toxic alcohol  25 mg/dL
adjuncts for methanol poisoning
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
Adjuncts for Ethylene Glycol Poisoning

O

O

O

C-OH

C-OH

C-OH

LDH

H-C-OH

H-C-H

H-C-OH

H

O

O

Glyoxylic Acid

Glycolic Acid

Oxalic Acid

B1, Mg2+ B6

-OH- Ketoadipic Acid Glycine + Benzoic Acid

Hippuric Acid

LDH = Lactate dehydrogenase

adjuncts for ethylene glycol poisoning35
Adjuncts for Ethylene Glycol Poisoning
  • To enhance metabolism away from oxalates*
    • Thiamine 100 mg every 4- 6 hours
    • Pyridoxine 50 mg every 4-6 hours

* Limited data

diethylene glycol
Diethylene Glycol
  • Elixir of Sulfanilamide disaster 1937-38
  • Renal failure 105 deaths
  • U.S. Legislation of Drug Safety
benzyl alcohol
Benzyl Alcohol
  • Preservative in some medications
  • Gasping Baby Syndrome
    • Potentially fatal in neonates

H

H-C-OH

Benzyl Alcohol

isopropanol
Isopropanol
  • Metabolized to acetone
  • No acidosis
  • Supportive care

H

H-C-H

H-C-OH

H-C-H

H

Isopropanol

3C

glycol ethers
Glycol Ethers
  • Brake fluid
  • Solvents
  • Rarely metabolized to ethylene glycol
  • Supportive care
propylene glycol
Propylene Glycol
  • Metabolized to lactate
  • Acidosis in ingestion
  • IV as diluent QRS widening, hypotension*

H

H-C-OH

H-C-OH

H-C-H

H

Propylene Glycol

* Phenytoin diluent

summary
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