08/06/2025
Special thanks to Dr. Mike Moss for the next Tox case!
Case
A 62 year old M presented to the ED after being found down by bystanders. He was confused but stated he drank “brake fluid.”
He was obviously tachypneic and hypoxic with initial sats in the low 80s. Initial blood gas showed pH 6.83, pCO2 36.8, HCO3 5.8, and lactate 9.3. A serum lactate was 7.3. Serum osmolality was 338 with a calculated osmolal gap of 37.
He was treated with fomepizole, sodium bicarbonate, pyridoxine, thiamine, and folate. He was admitted to the MICU and nephrology was consulted for emergent hemodialysis. He received 4 hours of conventional hemodialysis, though this was interrupted by a brain attack activation for unequal pupils as well as difficulties with the dialysis catheter.
Following hemodialysis, his serum osmolality had decreased to 314 and anion gap decreased from 32 to 18. He became more hypotensive requiring vasopressors and was switched to CRRT. By the next morning his osmolal and anion gaps had largely resolved, but CRRT and fomepizole were continued given the inability to measure diethylene glycol quickly. Ethylene glycol and methanol were undetectable. His creatinine remained somewhat elevated at 2.6, but he did not experience oliguria.
About one week after admission, his initial diethylene glycol resulted at 49 mg/dL which declined to 8.2 mg/dL following hemodialysis.
The patient remains ill with multiple complications of his critical illness.
Take Home Points
Multiple other toxic alcohols, besides ethylene glycol and methanol, are found in a wide variety of products and may also cause acidosis and nephrotoxicity
Diethylene glycol, found in some brake fluids, causes acidosis and nephrotoxicity
Treatment includes fomepizole to block metabolism and hemodialysis to remove toxic metabolites
Diethylene Glycol
Diethylene glycol (DEG) has an unfortunate history of causing multiple large-scale outbreaks of acidosis, renal injury, and death around the world. Most famously, an outbreak of over 100 poisoning deaths in 1937 from use of DEG as a diluent in children’s sulfanilamide elixir was the impetus for establishing the United States FDA in the 1938 Food, Drug, and Cosmetic Act.
Though its toxicity has long been recognized, DEG continues to cause poisonings when unscrupulous pharmaceutical manufacturers substitute it for safer alternatives. At least 16 separate clusters have occurred since 1937 with the most recent occurring in The Gambia in 2022 (Bastani 2023).
DEG is used in a variety of applications but is most readily encountered by the average patient in DOT 3 and 4 brake fluids.
Chemically, DEG is a dimer of ethylene glycol. However, it is not metabolized into ethylene glycol. Similar to other alcohols, it is metabolized sequentially by alcohol and aldehyde dehydrogenase to diglycolic acid (DGA). This metabolite is directly nephrotoxic, and may cause renal necrosis by chelating calcium or inhibiting succinate dehydrogenase. Similar mechanisms may be responsible for hepatotoxicity and neurotoxicity that occurs in some cases.
Diagnosis is primarily by history. An elevated osmolal gap may be present early in the course of toxicity, though it must be interpreted with caution. The osmolal gap is a relatively insensitive test, and a patients baseline osmolal gap is unknown. A “normal” osmolal gap could include 15-20 mOsm of a toxic alcohol. Serum concentrations are only available at specialized laboratories, often with long turn around times. Little is known about toxic concentrations of DEG in serum in humans. Toxic doses are roughly estimated at 1 mL/kg of 100% DEG. Brake fluids contain about 15-25% DEG.
Treatment is with fomepizole to inhibit alcohol dehydrogenase and prevent metabolism to the toxic DGA. Data on removal by hemodialysis is limited, with a single case report finding a decline from the very low level of 1.6 mg/dL to undetectable after HD (Brophy 2000). However, given its low volume of distribution, lack of protein binding, and low molecular weight it is likely dialyzable. Hemodialysis should be considered in most any patient with DEG poisoning, as there is limited data on fomepizole monotherapy. Dialysis is recommended in any patient with severe toxicity, acidosis, or renal injury.
Given the rare and unusual nature of DEG poisoning, consult with a toxicologist or poison center in all cases.
References
Bastani P, Jammeh A, Lamar F, et al. Acute Kidney Injury Among Children Likely Associated with Diethylene Glycol–Contaminated Medications — The Gambia, June–September 2022. MMWR Morb Mortal Wkly Rep 2023;72:217–222. DOI: http://dx.doi.org/10.15585/mmwr.mm7209a1
Brophy PD, Tenenbein M, Gardner J, Bunchman TE, Smoyer WE. Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kidney Dis. 2000 May;35(5):958-62. doi: 10.1016/s0272-6386(00)70270-8. PMID: 10793034.
Schep, L. J., Slaughter, R. J., Temple, W. A., & Beasley, D. M. G. (2009). Diethylene
