Chapter 153 Toxic Alcohols

Methanol
Sources: antifreeze, windshield wiper fluid, carburetor fluid, sterno,
glass cleaner, paint thinner
Toxic Dose: 0.15 cc/kg of 100% methanol
Pharmacology

Absorption: Rapidy absorbed with peak levels 30-60 minutes

post-ingestion. Volatile at room air inhalational toxicity

Metabolism:
Metabolized by alcohol dehydrogenase to formaldehyde,
which is metabolized to formic acid by aldehyde
dehydrogenase.
ADH metabolism is 1st order at lower levels and zero order
at higher levels, resulting in prolonged methanol levels
with larger ingestions
Ethanol has higher affinity for alcohol dehydrogenase than
methanol, so metabolism is delayed
Formic acid is metabolized to CO2 + H2O through a folatedependent pathway

Elimination: Small amount excreted in the lungs

Pathophysiology

Methanol irritation of the gastric mucosa

Formic acid:
Optic neuropathy: Muller cells (glial cells) in the retina
metabolize methanol to formic acid. The formic acid
disrupts cellular metabolism calcium influx, microtubule
dysfunction and mitochrondial dysfunction.
Putaminal necrosis: Postulated similar mechanism as optic
neuropathy
Methanol metabolism
Iron binding: Formic acid binds to Fe cytochrome
dysfunction with anaerobic respiration ( lactate)
Non-specific cellular injury: lipid peroxidation, free radicles, antioxidant reactions
Clinical Presentation

Symptom onset: Low affinity for ADH latent period of 12 24 hrs. if EtOH co-ingestion, if lg
ingestions.

Early symptoms:
CNS
LOC, confusion, ataxia
HEENT
Visual disturbances (central scotoma, snowstorm blindness), disc edema, RAPD
GI
AP, vomiting

Late symptoms:
CNS
Seizures, coma
Resp
Tachypnea
Metab
Metabolic acidosis
Ethylene Glycol
Sources: de-icing fluid, brake fluid, coolant, antifreeze
Toxic Dose: 0.2 cc/kg of 100% ethylene glycol
Pharmacology

Absorption: Rapidly absorbed when ingested with peak levels 1-4 hrs post-ingestion

Distribution: Lg Vd (like water)

Metabolism/Elimination
25% excreted unchanged by kidneys
Remainder is converted to glycoaldehyde, which is then converted to glycolic acid by aldehyde

dehydrogenase.
Glycolic acid is metabolized to glyoxylic acid, which is then broken down into:
Glycine (cofactor pyridoxine)
Oxalic acid
hydroxy ketoadipate (cofactor Mg2+ and thaimine)

Pathophysiology

Glycolic acid, glyoxylic acid and glycoaldehyde cause nephrotoxicity (ATN)

Oxalic acids forms crystals with Ca2+ involvement of various systems:

GU: Crystal nephropathy
CNS: Deposition of crystals in parenchyma, BVs punctate hemorrhage, edema and aseptic
meningoencephalitis
HEENT: Deposition of crystals in retina visual changes
MSK: Crystal deposition myonecrosis

Glycolic acid anion gap metabolic acidosis

Inhibition of citric acid cycle lactate (mild contribution to acidosis)

Clinical Presentation

Acute Neurologic Stage (30 min 12 hrs)

CNS
ataxia, confusion, nystagmus
GI emesis, AP

Cardiopulmonary Stage (12-24 hrs)

CVS
tachycardia, myocardial depression (hypotension)
Resp
tachypnea (d/t acidosis + ARDS)
Metab
Ca2+ d/t binding with oxalic acid
MSK
myositis rhabodomyolysis

Renal Stage (24 72 hrs)

GU AKI d/t ATN +/- pigment nephropathy, crystal nephropathy

Delayed Neurologic Sequelae Stage (6 12 days)

CNS
Cranial neuropathy is most common, but other abnormalities can occur (varying
severity)
Diagnosis
Osmolar Gap (Normal < 10 mmol/L)

Alcohols freezing point depression

Calculated osmoles = Na x 2 + glucose + BUN

To estimate the contribution by ethanol, multiply the alcohol level x 1.25 always check EtOH level.

Causes of OG:
Alcohols: ethanol, ethlyene glycol, methanol, isopropyl alcohol, propylene glycol
Sepsis & MODS
Ketotic states: AKA, DKA, SKA
Hyperlipidemia
Hyperproteinemia
Osmotic diuretics

OG 's as toxic alcohol is metabolized

Anion Gap (Normal < 14)

AG = Na (Cl + HCO3-)

Causes of anion gap

Congenital: Inborne errors of metabolism
Acquired:
Ketones: DKA, SKA, AKA
Uremia: renal failure
Lactate:
lactate production: hypoperfusion, cellular toxins (Fe, CO, CN, H 2S), hypermetabolic states
(seizures, hyperthermia), toluene
lactate metabolism: liver disease, metformin
Toxins:
toxic alcohols, ASA, paradehyde

Toxic Alcohol Levels

Measures level of parent compound, not metabolite, so may be falsely low if presenting late
Urinalysis

Presence of crystals (calcium oxalate crystals) is suggestive of ethylene glycol toxicity (occurs in <
50%)

Urinary fluorescence: Antifreeze additive may appear in urine, but high rate of false positive and false
negatives
EKG

QTc may be d/t hypocalcemia with ethylene glycol poisoning

Management
ABC's: Standard ACLS. Check chemstrip (especially in children).
Decontamination: Not effective d/t rapid absorption + dangerous d/t LOC
Specific Therapy:

Sodium Bicarbonate: Toxic products are weak acids so

normalization of serum pH ionized form of acids, which do not Indications for Antidotal
Therapy
cross physiologic membranes (ion trapping). Indicated when
serum pH < 7.3
Recent ingestion with OG >
Methanol: trapping of formate in the serum ( cellular uptake)
10
+ trapping of formate in urine ( excretion)
Methanol level > 15
Ethylene glycol: trapping of glycolate in the urine ( excretion)
mmol/L and ethylene glycol

Ethanol: Competitively inhibits alcohol dehydrogenase, which a

level > 8 mmol/L
much greater binding affinity then either methanol or ethylene
Strong clinical suspicion +
glycol. ADH blockade very slow metabolism of toxic alcohols by
2 of pH < 7.3, HCO3- < 20,
other means.
OG > 10 and/or oxlate
Dosing:
crystals in urine
Loading dose is 0.8 g/kg (For PO: Proof = percent EtOH x
2)
Maintenance dose:

Non-drinker: 0.6 1.5 cc/kg/hr (10% EtOH)

Drinker: 1.5 2 cc/kg/hr

Hemodialysis: 3 5 cc/kg/hr
Target level: Serum EtOH > 100 mg/dL
Complications: hypoglycemia, volume overload, LOC

Fomepizole: Long acting competitive inhibitor of alcohol dehydrogenase

Indications:
History: Known ingestion
Dosing: Given q12 h x 4 doses

Adjunctive Treatments: Goal to shunt metabolism of toxic alcohols down less toxic pathways by
providing substrate
Ethylene glycol: vitamin B6, thiamine
Methanol: folate or folinic acid (leukovorin)

Dialysis: Indications for dialysis:

Absolute levels: Methanol > 15 mmol/L or ethylene glycol > 8 mmol/L
Hemodynamic instability
Metabolic acidosis (pH < 7.25) that is refractory to treatment
Electrolyte imbalance not responsive to conventional therapy
End-organ toxicitiy:
Renal impairment
Coma or severe obtundation
Visual abnormalities
Isopropanol
Sources: rubbing alcohol, de-icer, solvents
Toxic Dose: 2-4 cc/kg of 100% isopropanol

Pharmacokinetics

Absorption: rapidly absorbed

Metabolism/Elimination
Hepatic metabolism to acetone by alcohol dehydrogenase. T1/2 of acetone is 20 hrs. T1/2 of
isopropanol is 3-7 hrs (shorter in children)
20% excreted unchanged in the urine
Clinical Presentation
Early
CN
confusion, altered LOC, ataxia
GI
gastritis (may be significant)
Late
CNS
CVS
GU
MSK
Metab

LOC, coma
hypotension (with lg ingestions)
renal failure d/t ATN (rare)
atraumatic rhabomyolysis
Ketosis without acidosis (isopropanol acetone)

Investigations
Typical laboratory findings are an elevated osmol gap without acidosis.
False creatinine can occur b/c of cross-reactivity with acetone.
Watch for hypoglycemia, especially in children.
Management

Generally supportive no role for ethanol or fomepizole

IHD indicated if refractory hypotension (rare) or level > 400 mg/dL

Benzyl Alcohol
Sources: preservative in bacteriostatic NS and other IV medications
Pharmacokinetics: Metabolized to benzoic acid
Clinical Presentation: Neonates with excessive doses develop gasping baby syndrome: LOC, hypotension,
metabolic acidosis, gasping respirations, hepatic & renal failure MODS death
Glycol Ethers
Sources: brake fluids, solvents
Pathophysiology: May be metabolized to ethylene glycol, particularly in significant overdoses
Management: As for ethylene glycol
Propylene Glycol
Sources: dilutent for many drugs (dilantin, diazepam), anti-freeze
Pathophysiology: Metabolized to lactate and pyruvate anion gap metabolic acidosis
Clinical Presentation: May cause hypotension (cause of hypotension with IV dilantin)
Management: Supportive
Diethylene Glycol
Sources: power steering fluid, brake fluid
Pathophysiology:

Parent compound renal failure (cortical necrosis)

Metabolized to hydroxyethoxy acetic acid, which can cause an anion gap metabolic acidosis
Management: Hemodialysis