Toxic alcohols

What is the anion gap equation?

anion gap = Na+ - (Cl- + HCO3-)

what is a normal anion gap?

~4-12

What things cause increased anion gap metabolic acidosis?

Methanol

Uremia

DKA, SKA, AKA (diabetic, starvation, alcoholic - acidosis)

Phenformin (metformin), paraldehyde

Isoniazid, INH

Lactate, CO, CN, methemoglobinemia

Ethylene glycol

Salicylates

what are the toxic alcohols?

methanol, ethylene glycol, and isopropanol (isopropyl alcohol)

Clinical presentation of toxic alcohol use

altered mental status (inebriation), GI distress

T/F: there are specific clinical presentation differences between toxic alcohols

true

where is methanol found/used for?

Gas-line antifreeze, windshield washer fluid, denaturants

Does methanol have high volatility?

yes - can be ordered/show up on a volatile’s panel

what is ethylene glycol used for?

automobile coolant, solvents, de-icers, and in air conditioning units

Does ethylene glycol have high voltatility?

No

what are the early features of methanol toxicity?

possible GI distress/inebriation within 0-24 hours of ingestion

what are the early features of ethylene glycol toxicity?

possible GI distress/inebriation that may be more delayed than methanol toxicity

what are the clinical presentations that occurs later in methanol toxicity?

high anion gap metabolic acidosis and visual changes (blindness)

Why can methanol cause blindness

due to the formation of formaldehyde and formic acid (formic acid is extremely toxic to the optic nerve and the retina)

what are the clinical presentations that occurs later in ethylene glycol toxicity?

high anion gap metabolic acidosis, nephrotoxicity, and hypocalcemia 

T/F: the higher the anion gap the more severe the toxicity/the longer it has been since exposure to toxic alcohols

true

T/F: ethanol can inhibit alcohol dehydrogenase

true

T/F: methanol metabolism to formic acid is the biggest toxicity cocern

true

What is methanol metabolized to?

formaldehyde —→ formic acid & formate

what is ethylene glycol metabolized to?

glycolic acid —→ glyoxylic acid —> a bunch of acids (ketoadipic acid, oxalic acid, hippuric acid, benzoic acid)

what is the initial management for methanol and ethylene glycol?

GI contamination (but not very helpful), electrolytes and arterial blood gas, ethanol level, methanol and ethylene glycol levels (delayed in receiving results), measure osmolality, consider ADH inhibition 

why is GI decontamination not helpful for toxic alcohol ingestion?

alcohols are absorbed extremely fast so whole bowel irrigation doesn’t work, and charcoal cannot bind with alcohol

dosing of ethanol for methanol and ethylene glycol overdose

1 g/kg —- IV 10% solution or PO equivalent of 4 shots patron

What is the maintenance dosing for ethanol in methanol/ethylene glycol overdose

up to a BAC of ~100 mg/dL (legal limit is 80 mg/dL)

what are the ADH inhibitor options?

ethanol and fomepizole

MOA of fomepizole

competitive inhibitor of alcohol dehydrogenase

ADRs of foempizole

HA, nausea, dizziness, minor allergic reactions (rare)

dosing of fomepizole

loading dose of 15 mg/kg

second phase of 10 mg/kg Q12h for 4 doses

Maintenance phase of 15 mg/kg Q12h

Why do the dosing phases of fomepizole go from high to low back to high doses?

the medication has autoinduction!

how is fomepizole diluted for administration?

diluted in NS or D5W and infused over 30 minutes

T/F: you need to increase the dose of fomepizole during hemodialysis

true

facts regarding ethanol use compared to fomepizole:

inexpensive, difficult to dose/titrate/prepare (especially oral), hypotonic, limited availability, and ADRs of CNS inebriation, thrombophlebitis, GI sx’s

facts regarding fomepizole use compared to ethanol:

expensive, easy to dose quickly, minimal adverse effects

why is sodium bicarbonate used in ethylene glycol toxicity?

to correct acidosis

why is sodium bicarbonate used in methanol toxicity?

to correct acidosis, reduce ratio of formic acid to formate, and promote ion trapping

when would hemodialysis be used for methanol toxicity?

levels of 50 mg/dL (or higher) or levels > 70 mg/dL if fomepizole was used

when would hemodialysis be used for ethylene glycol toxicity?

levels of 62 mg/dL (or higher) or levels > 310 mg/dL if fomepizole was used

when would hemodialysis generally be used for toxic alcohols?

high osmol gap without another cause, end organ manifestations of toxicity, severe metabolic acidosis (pH < 7.15)

since toxic alcohol levels may take a while to get back what can be used to determine pt severity?

osmol gap and lactate/ketone/renal function measurements

T/F: earl in toxic alcohol ingestion the osmol gap will be elevated

true

how to calculate osmolality:

2Na + BUN/2.8 + glucose/18 

how is the osmol gap calculated?

measure osmolality - calculated osmolality = osmol gap

what is an osmol gap?

similar concept to anion gap — an attempt to indentify alcohol/N or other unaccounted for osmols

T/F: a normal osmol gap is useless

true

what is a normal osmol gap?

-14 to +10

why is a normal osmol gap useless?

Such variability in normal osmol gap may equate to dialyzable level that appears normal

T/F: a high osmol gap without other causes is very useful

true

which acid contributes the high anion gap with methanol ingestion?

formic acid

which acid contributes the high anion gap with ethylene glycol ingestion?

glycolic acid

which major acids are measurable?

lactic acidosis (lactate) and keto acidosis (ketoacids)

which major acids are exogenous and are not measurable readily/quickly?

glycolic acidosis and formic acidosis

If a patient presents with metabolic acidosis, an increased anion gap, and increased ketones, what should be suspected?

DKA, SKA, AKA, salicylates

If a patient presents with metabolic acidosis, an increased anion gap, and increased lactate, what should be suspected?

medical causes (seizures, sepsis), toxin causes (phen(met)formin, INH, salicylates)

If a patient presents with metabolic acidosis, an increased anion gap, and worsened renl function, what should be suspected?

consider uremia

If a patient presents with metabolic acidosis and an increased anion gap, but nothing else (no elevated ketones/lactate) what should be suspected?

formic acid or glycolic acide

what is propylene glycol?

environmentally safe antifreeze, drug diluent (lorazepam, diazepam, phenytoin)

what is propylene glycol metabolized to?

lactic acid (will elevate lactate)

Why are we not as concerned about the elevated lactate seen with propylene glycol?

because the patients are metabolically okay which is different from high lactate seen in sepsis

what is isopropyl alcohol

“rubbing alcohol” that is very inebriating and irritating 

what are we concerned about with isopropyl alcohol ingestion?

hemorrhagic gastritis and significant GI bleeding

what is isopropyl alcohol metabolized to?

acetone

which alcohol presents are ketosis without acidosis?

isopropyl alcohol

why does isopropyl alcohol cause ketosis without acidosis?

is metabolized to acetone which is a ketone derivative but does not have a proton to cause acidosis

what is the overall treatment plan for suspected toxic alcohol toxicity?

give ADH inhibition (fomepizole), consider hemodialysis, give adjunctive therapies as indicated/needed

when would sodium bicarb be good to use?

in acidosis for ion trapping

when would folic acid supplementation be used?

methanol toxicity

when would magnesium supplement be used?

ethylene glycol toxicity

when would thiamine supplementation be used?

ethylene glycol toxicity

when would pyridoxine (B6) be used?

ethylene glycol toxicity

T/F: the osmol gap can help rule in a toxic alcohol ingestion but may not be able to rule out one

true

T/F: isopropyl alcohol is not as toxic as other toxic alcohols

true