One of our readers has asked to have this question addressed. It is a good subject as the treatment is based on an understanding of the toxicity and the laboratory results. Ethylene glycol ingestion occurs more frequently in TN than in most other states. I will address it in two parts.
Ethylene glycol is a colorless, odorless liquid found in antifreeze.
Once ethylene glycol is ingested, it is rapidly absorbed with peak concentrations occurring one to four hours after ingestion.
Metabolism occurs in the liver and the kidney. Ethylene glycol itself is nontoxic. The toxicity of ethylene glycol is due to its’ four metabolic products which are:
1) aldehydes which inhibit oxidative phosphorylation, respiration, and glucose metabolism,
2) glycolic acid which contributes to acidosis
3) oxalic acid which chelates calcium and is deposited as calcium oxalate crystals in tissue
4) lactic acid which contributes to acidosis
The metabolic pathway is as follows:
alc. deh. ald. deh. ↑ Thiamine
Ethylene Glycol ———> Glycoaldehyde ———> Glycolic acid ———> Glyoxylic acid ———> Oxalic acid
alc = alcohol
ald = aldehyde
deh = dehydrogenase
The primary metabolic effect is an anion gap acidosis that occurs from the formation of glycolic and lactic acids.
Hypocalcemia occurs due to calcium-oxalate binding. Calcium oxalate crystals are found in many tissues on post-mortem exam.
Glycoalate is the primary renal toxin. One of the causes of acute oliguric renal failure is deposition of calcium oxalate in the proximal tubules. This may also cause hydronephosis and ATN.
Ethylene glycol causes a brief period of inebriation. Untreated, the increasing acidosis causes hyperventilation, coma, seizures, cerebral edema, pulmonary infiltrates and oligouric renal failure (16-48 hours post ingestion). If a lethal dose has been ingested and the patient is untreated, death from multiorgan failure usually occurs within 24-36 hours after ingestion.
Serum ethylene glycol concentrations are not available in most hospitals. Measurement of osmols is more readily available.
Sodium and its anions are the osmotically active particles in the serum and are the basis for the calculation of serum osmolarity. An osmolar gap greater than 10 should make one consider low molecular weight osmotically active particles such as ethanol, methanol, ethylene glycol, and mannitol. The analytic methodology is important. Osmality must be determined by freezing point depression to detect ethylene glycol serum osmols as the vapor pressure method cannot detect volatile alcohols.
Calculated Osm: 2Na +BUN/2.8 + glucose/18 + ethanol/4.6
Osmolar gap is the difference between the Measured Osm and the Calculated Osm.
Hypocalcemia must be present. (EKG changes may reflect this)
Anion gap reflects accumulated glycoalate and is somewhat prognostic
Renal function should be followed.
Urinalysis may reveal blood and protein as well as calcium monohydrate or dihydrate crystals. Some antifreeze products contain sodium fluorescein as a colorant. If this is the case, the urine will fluoresce under a Wood’s lamp. Lack of crystals or fluorescence does not rule out ethylene glycol ingestion.
Ethylene glycol is ingested. Increase in measured serum osmolality reflects the amount of ethylene glycol that has been absorbed into the blood. The measured osmolality does not reflect the ethylene glycol that has yet to be absorbed or has already been metabolized. Fortunately ethylene glycol is absorbed quite rapidly so ethylene glycol absorption need only be considered for the first couple of hours after arrival.
The acidosis reflects the ethylene glycol that has been metabolized. A patient with a significant acidosis and no osmolar gap has no ethylene glycol to be metabolized. A patient with a large osmolar gap and no acidosis has not metabolized any of the ethylene glycol. Understanding these concepts is the basis for treatment recommendations.
Next week: Part II; Ethylene Glycol Treatment and Considerations
I am interested in any questions you would like answered in the Question of the Week. Please email me with any suggestion at Donna.Seger@Vanderbilt.edu.
Donna Seger, MD
Tennessee Poison Center