Toxic Alcohols

• EB Medicine Review
• Calculating Osmal Gap of Fluids

Best Osmal Gap Formula

Plasma osmolality = (Na + K + Cl + lactate + glucose (convert) + urea + HCO3 + 6.5) x 0.985 (Inten Care Med 2013;39:302)

Consider if Osmal Gap

Positive osmal gap >10 (2 Na + Gluc/18 + BUN/2.8 + ETOH/3.7) ETOH/4.6, Ethylene Glycol/6.2, Methanol/3.2, Isopropanol/6.0, Propylene Glycol/7.6 (Ann Emerg Med 1996;27) Also Acetone can cause osmal gap. Normal gap is considered <10, but ranges from -14 to 10, so a pt with a low baseline can be toxic with a gap less than 10 (this is crucial, a negative osmal gap does not rule out toxic etoh ingestion)   Causes of high osmal gap ME DIE Methanol Ethylene glycol Diuretics (osmotic diuretics like mannitol) Isopropyl alcohol Ethanol   also: renal failure sepsis mannitol hyperlipidemia hyperproteinemia Propylene Glycol     The authors correctly ascribe hyponatremia in these two cases to a physiologic shift of intracellular water to the extracellular volume in response to the osmotic pressure gradient imposed by hyperglycemia. Consequently, the osmolality of serum is somewhat dampened and the sodium concentration is decreased. It is commonly accepted that the serum sodium concentration decreases approximately 1.6 mmol/L for each 100 mg/dL increase in glucose above a nominal value of 100 mg/dL (2). However, a value of 2.4 mmol/L decrease in sodium per 100 mg/dL increase in glucose may be more appropriate (3). Moreover, the authors accurately state that sodium measurements in such cases are true and reflect the physiologic dilutional effect of the hyperosmolality. Our data confirm analytical accuracy (± 1 mmol/L) for sodium at glucose concentrations up to 2500 mg/dL (unpublished data). In contrast, falsely low sodium values (pseudohyponatremia) may result from the volume exclusion effect due to very elevated triglycerides or protein when sodium is measured by indirect methods (those requiring a dilution step) but not when measured by direct (no dilution) methods (4). 3 T.A. Hillier, R.D. Abbott and E.J. Barett, Hyponatremia: evaluating the correction factor for hyperglycemia, Am J Med 106 (1999), p. 399.

Isopropyl (Rubbing, etc.)

Twice the CNS depressant as ETOH Metabolized to Acetone (ketone but not a ketoacid) Ketosis s acidosis Gastrointestinal symptoms are

prominent, including nausea, vomiting, hematemesis, and abdominal pain Acetone levels interfere with accurate Cr Just supportive care can d/c 2 hours after return to baseline     DID YOU KNOW THAT… isopropyl alcohol ingestion can falsely elevate the serum creatinine? There have been reports of “pseudo”-renal failure in patients who ingest isopropyl alcohol. A false elevation in serum creatinine can occur due to acetone interfering with the creatinine colorimetric assay. Using an enzymatic assay, such as that used in a blood gas analyzer, instead of the colorimetric assay will avoid the acetone interference and give a rapid and accurate measure of the patient’s serum creatinine.   If pt has an ETOH level >100 mg/dl and they look sick it is prob not from toxic alcohol unless they somehow took a bunch of toxic alcohol, waited for metabolism and then drank etoh. Tox alcohol patients will also get sicker on rechecks

Isopropyl will cause an osmal gap. It fits into the formula if you divide isopropyl in mg/dl by 6

Methanol (Wood, printers, painters, antifreeze, windshield)

Metab by alcohol dehyrog to formaldehyde then aldehyde dehydrog takes it to formic acid Blocks oxidative phosphorylation so you get lactic acidosis, can be severe Presents with abd pain and vision changes (snowfield vision)

Causes blindness, brain hemorrhage and GI c/o

Give Folate b/c it is a cofactor in the reduction of formic acid to CO2  Get Methanol Levels

ethanol to maintain 100-150 or fomepizole

folate Patients with levels >0.5 g/l should probably be dialyzed even with fomepizole treatment Review (Intensive Care Med 2005;31:189)

Current Recommendations for Methanol

Ethylene Glycol (Antifreeze)

Tastes sweet, methanol does not Metabolized to Oxalic Acid, thiamine deficiency contributes Severe acidosis mainly due to glycolic acid CNS, Cardio, Renal, ARDS Also hypocalcemia from oxalate precipitation, can be severe enough to cause EKG changes and conduction abnormalities Look at urine c woods lamp Disk pallor on fundoscopic exam Get ethanol level, if elevated, toxicity will be delayed Correct pH if less than 7.2 Ethanol to maintain levels between 100-150 10 mL/kg of 10% ethanol followed by a maintenance infusion of 1.5 mL/kg/h will usually maintain therapeutic levels (shoot for 100) +- Dialysis (Triple Etoh Dosing) levels >25 for both methanol and ethylene glycol Thiamine, Pyridoxine Experimental-4-methylprazole fomepizole 15 mg/kg intravenously is administered followed by doses of 10 mg/kg every 12 hours until serum levels fall below 20 mg/kg clearnace should be rapid in the absence of renal fx   can falsely show up as lactate since glycolate, a metabolite, has almost the same chemical structure (Inten Care Med 2006;32:626)

Benzyl Alchol

Preservative in NS and other IV meds benzoic acid+glycine=hippuric acid neonatal gasping synfrome

Propylene Glycol

Found in sierra antifreeze and diluent for diazepam and glucagons Metabolized to lactate

Diethylene Glycol

sweet tasting Chinese company used it instead of glycerine and killed a bunch of folks used in brake fluid and the fluid in fog machines Glycol ether we do not know if it is the parent compound or metabolite so no fomeprazol     administration of ETOH 8 cc/kg of 10% solution shoot for etoh levels 100-200 mg/dL       | | |