Occupational poison exposures reported to a poison center helpline, Colorado, 2000-2010
Toxic Alcohols Rama B. Rao Bellevue/NYU Medical Center New York City Poison Control Center.
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Transcript of Toxic Alcohols Rama B. Rao Bellevue/NYU Medical Center New York City Poison Control Center.
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
• 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 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
• 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
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
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