The Hook: Description of Toxicity
Two patients, Duke and Hippo, presented to DoveLewis for ingestion of ethylene gylcol.
Ethylene Glycol (EG) is a life threatening, rapidly metabolized toxin found in automotive antifreeze solutions, industrial coolants, and various household products (usually in too small a quantity to be significant). EG is metabolized by alcohol dehydrogenase into various acid metabolites, with oxalic acid being the final metabolite that binds with calcium leading to crystallization of renal tubules. Central nervous symptoms (CNS) such as ataxia, paresis, mentation changes, as well as gastrointestinal signs can be seen in less than 1 hour. While initial symptoms of intoxication may wane after 4 - 6 hours, metabolic acidosis occurs within 12 hours, followed by anuric renal failure in 72 hours.
Various EG assays exist. DoveLewis works with a local human toxicology lab that offers 24/7 (STAT) EG testing (gas chromatography), allowing for quantitative levels. This method also helps prevent false positives from other sources (propylene glycol in midazolam, inappropriate sample handling, etc.) Various alcohol compounds may interfere with other forms of testing so care should be taken to understand the limitations of your assay.
Various secondary blood work abnormalities can be seen as ethylene glycol is metabolized. The primary acidic metabolites, which cannot be measured by in-house laboratories, can cause increases in serum osmolality, osmolar and anion gap leading to severe metabolic acidosis. Hyperphosphatemia may occur early if the ethylene glycol containing fluid also contains a phosphate-based rust inhibitor, or may occur later as a consequence of renal failure. Hypocalcemia is common, however clinical signs due to hypocalcemia are rare. Lactate may be falsely elevated due to metabolites being measured as lactate, or it may be truly elevated due to hypoperfusion. Acute renal failure, with increases in BUN, creatinine, Phosphorus and potassium generally occurs 24-72 hours post ingestion.
Urine specific gravity is usually decreased due to the osmotic diuretic effect of ethylene glycol (1.008 - 1.012- after 3 -4 hours). Development of calcium oxalate crystalluria (either monohydrate or dihydrate) can occur 6 hours post ingestion. Ultrasonographic changes to the renal parenchyma (“halo sign”) can be an indication of EG toxicity.
The Good Part: Therapeutic Options
Since gastric decontamination is often ineffective due to the rapid absorption and limited efficacy of activated charcoal, initial therapy often focuses on antidotal therapy (ethanol or fomepizole) to prevent the formation of active metabolites and allow excretion of ethylene glycol unchanged, or extracorporeal therapy (continuous renal replacement therapy, hemodialysis) to remove both the ethylene glycol and its metabolites. Because it can remove both ethylene glycol and metabolites, extracorporeal therapy is recommended with severe intoxications, or when circulating metabolites are suspected.
Hippo’s blood was processed quickly but with no detectable EG. Considering that he was symptomatic with a known ingestion, a second EG level was submitted to ensure reduced risk of a false negative due to progressive EG absorption 4 hours after the initial level was drawn.
The Conclusion: Clinical Resolution
Due to extremely elevated levels of EG on Duke’s initial blood sample, and fomepizole being unavailable, the decision was made to institute extracorporeal therapy. Two continuous renal replacement therapy (CRRT) treatments were performed, with the initial therapy dropping EG levels profoundly. While patients levels were still detected at 36mg/dl after the second session, the values were below a cutoff and effective range of 50mg/dl. He was then transitioned to IV diuresis.
Prognosis is fair to good with antidotal and extracorporeal therapy initiated with 4 - 6 hours of ingestion. Therapy initiated post 8 - 12 hours is much more guarded, with patient exhibiting symptoms of azotemia, or ultrasonographic abnormalities having a more poor to grave prognosis.
Both Duke and Hippo were discharged from the hospital with normal renal parameters, unremarkable physical examination, and normal mentation.
Ethylene glycol can be highly fatal if left untreated and clinical symptoms can often be misleading from other toxicities (marijuana, etc). Thorough medical history, physical examination, appropriate initial diagnostics, and rapid therapy can drastically improve the outcomes of these patients.