Download Toxic Alcohols

Toxic Alcohols
Rama B. Rao
Bellevue/NYU Medical Center
New York City Poison Control Center
Alcohols: R-OH
OH
H
H-C-OH
H
Methanol
1C
H
H-C-H
H-C-OH
H-C-H
H-C-OH
H
Ethanol
2C
H
Ethylene Glycol
2C
Alcohols: R-OH
H
H-C-H
H
H-C-OH
H-C-OH
H-C-OH
H-C-H
H-C-H
H
H
Isopropanol
3C
Propylene Glycol
3C
H
H-C-OH
Benzyl Alcohol
Ethanol
OH
H-C-H
H-C-H
H
Ethanol
O
C-H
ADH
H-C-H
H
Acetaldehyde
ADH = Alcohol Dehydrogenase
ALDH = Aldehyde Dehydrogenase
O
ALDH
C-OH
H-C-H
H
Acetic Acid
Methanol
• Molecular weight 32
H
• Low freezing point
H-C-OH
H
• Highly volatility
Methanol
Methanol
• Gas Line Antifreeze
100%
• Windshield washer
fluid 30%
• Varnish removers
• Fuel for food
warming 3-70%
• Industrial uses
Methanol Metabolism
H
H-C-OH
H
Methanol
O
ADH
H-C-H
H
Formaldehyde
ADH: Alcohol Dehydrogenase
ALDH: Aldehyde Dehydrogenase
O
ALDH
H-C-OH
H
Formic Acid
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
H
H-C-OH
• Low Volatility
• High boiling point
H-C-OH
H
Ethylene Glycol
Ethylene Glycol
• Coolant/Antifreeze
• Solvents
• De-Icer
Ethylene Glycol Metabolism
H
H-C-OH
H-C-OH
H
Ethylene Glycol
O
ADH
C-H
O
ALDH
C-OH
H-C-OH
H-C-OH
H
Glycoaldehyde
H
Glycolic Acid
ADH = Alcohol dehydrogenase
ALDH = Aldehyde dehydrogenase
Ethylene Glycol Metabolism
O
C-OH
LDH
O
O
C-OH
C-OH
H-C-OH
H-C-H
H
Glycolic Acid
O
Glyoxylic Acid
B1, Mg2+
-OH- Ketoadipic Acid
H-C-OH
O
Oxalic Acid
B6
Glycine + Benzoic Acid
Hippuric Acid
LDH = Lactate dehydrogenase
Ethylene Glycol Toxicity
• Onset 4-6 hours
• Anion gap
acidosis
pH
• Tachypnea
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:
NG Tube
• Prevent metabolism or parent
compound to toxic metabolite
ADH Inhibition
• Enhance elimination
Substrates/Other
– Parent
– Metabolites
• Correct Derangements
Hemodialysis
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
• Acidosis indicates advanced
poisoning
• Lactate usually low*
• Patients with acidosis should
receive treatment
*Some glycolates are misidentified as lactate
Adjunctive Information:Ethanol
• Serum ethanol
inhibits metabolism
of EG and Methanol
• Onset of toxicity
EG/Methanol may
be delayed
Adjunctive Information: Osmol Gap
• Osmol Gap = Measured-Calculated Osmols
• Calculated:
2 Na + BUN + Glucose + Alcohol
2.8
18
N
• N = MW Alcohol/10
• Must use freezing point depression
Osmol Gap: Limitations
• Normal Osmol gap in
between – 14 ± 10
Osmol Gap
• Normal Osmol Gap in
setting of poisoning
does not rule out a
treatable level
Anion Gap
• Osmol Gap diminishes
as parent compound is
metabolized
Time
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
Treatment
Methanol
Ethanol
ADH
Aldehyde
ALDH
Ethylene Glycol
• Ethanol more avid for ADH
– 6-8x more avid than ethylene glycol
– 4x more avid than methanol
Acid
Ethanol
• Concentration = Dose
Vd (wt in kg)
• Vd of ethanol = 0.6 L/kg
• Desired concentration 100-200 mg/dL
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
O
C-OH
LDH
O
O
C-OH
C-OH
H-C-OH
H-C-H
H
Glycolic Acid
O
Glyoxylic Acid
B1, Mg2+
-OH- Ketoadipic Acid
H-C-OH
O
Oxalic Acid
B6
Glycine + Benzoic Acid
Hippuric Acid
LDH = Lactate dehydrogenase
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
• Elixir of Sulfanilamide
disaster 1937-38
• Renal failure 105 deaths
• U.S. Legislation of
Drug Safety
Benzyl Alcohol
• Preservative in some
medications
H
H-C-OH
• Gasping Baby
Syndrome
– Potentially fatal in
neonates
Benzyl Alcohol
Isopropanol
• Metabolized to
acetone
H
H-C-H
H-C-OH
• No acidosis
H-C-H
H
• Supportive care
Isopropanol
3C
Glycol Ethers
• Brake fluid
• Solvents
• Rarely metabolized to
ethylene glycol
• Supportive care
Propylene Glycol
• Metabolized to
lactate
• Acidosis in ingestion
H
H-C-OH
H-C-OH
H-C-H
• IV as diluent QRS
widening,
hypotension*
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