Ethylene glycol (EG;CAS No. 107-21-1) is the toxic chemical found in automotive antifreeze. Ethylene glycol is a frequently encountered etiology of human poisoning and causes significant morbidity and mortality. In 2002, 5816 calls to US Poison Control Centers involved human exposure to ethylene glycol. The medical management of presumed ethylene glycol poisoning involves a significant delay of several hours while waiting for confirmatory testing for EG in a serum sample;this testing is available only at reference laboratories. As the same time, an expensive antidote (fomepizole;4-methylpirazole;AntazolTM, Paladin Labs, Delaware US) and/or invasive empirical treatment (hemodialysis) must be started to prevent renal failure, worsening metabolic acidosis and death. While a reliable and validated qualitative ethylene glycol test kit (EGT, PRN Phramacal, Pensacola, FL) exists for use in veterinary medicine, the clinical management of EG poisoning in humans is not as advanced. Thus, EG poisoning diagnosis is hampered by the absence of a readily available screening test in nearly all hospital laboratories. The veterinary EGT has demonstrated efficacy in a small convenience sample of known EG positive serum samples. In that study (n=24), the EGT had 100% sensitivity and high specificity over a clinically relevant range of EG serum concentrations (27-281 mg/dl). No interference was observed in samples positive for methanol or ethanol. We propose an un-blinded, prospective, case-control study of the clinical utility of the veterinary EG test kit to detect ethylene glycol in human serum samples from known poisoning cases compared to unmatched controls. EGT kit results will be compared against criterion standard testing with gas chromatography/mass spectroscopy performed in duplicate at two independent reference laboratories. We will assess the EGT detection limit in human serum and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of the platform, as well as any evidence of interfering substances (ethanol, acetone, lactate, methanol, salicylate) leading to false positive or false negative results. If successful, this pilot study will provide preliminary data which will enable pursuit of a much larger, multi-centered, prospective, case controlled clinical trial, of the utility of the EGT kit.
Ethylene glycol is a fairly common occurrence and delay in diagnosis and treatment is a source of significant morbidity and mortality. Gas chromatography/mass spectroscopy (GC/MS), the current gold standard for the diagnosis of EG poisoning, is unfortunately not widely clinically available and confirmation of poisoning takes anywhere between 12 and 24 hours to be completed. Veterinarians have been using a qualitative EG assay in animals that ingest EG which is rapid, inexpensive, and easy to perform;our study will assess the utility of this bioassay in humans with clinical and laboratory suspicion of EG poisoning.