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 postingestion. 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
Methanol metabolism
neuropathy
◦ 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
▪ α hydroxy β 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:

◦
◦
◦
◦
◦
◦
OG
Alcohols: ethanol, ethlyene glycol, methanol, isopropyl alcohol, propylene glycol
Sepsis & MODS
Ketotic states: AKA, DKA, SKA
Hyperlipidemia
Hyperproteinemia
Osmotic diuretics
↓'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, H2S), 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 cross physiologic
membranes (ion trapping). Indicated when serum pH < 7.3
◦ Methanol: trapping of formate in the serum (↓ cellular uptake) +
trapping of formate in urine (↑ excretion)
◦ Ethylene glycol: trapping of glycolate in the urine (↑ excretion)

Ethanol: Competitively inhibits alcohol dehydrogenase, which a much
greater binding affinity then either methanol or ethylene glycol. ADH
blockade → very slow metabolism of toxic alcohols by other means.
◦ Dosing:
▪ 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
◦ 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
Indications for Antidotal
Therapy



Recent ingestion with OG > 10
Methanol level > 15 mmol/L
and ethylene glycol level > 8
mmol/L
Strong clinical suspicion + 2 of
pH < 7.3, HCO3- < 20, OG > 10
and/or oxlate crystals in urine
toxic pathways by providing substrate
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