Abstract
Introduction
Ethylene glycol (EG) is a frequently considered toxicant in poisoned patients. Definitive diagnosis relies on gas chromatography (GC), but this is unavailable at most hospitals. A glycerol dehydrogenase (GDH)-based assay rapidly detects EG. A rapid turnaround time and wide availability of necessary instrumentation suggest this method could facilitate the rapid detection of EG.
Methods
This is a prospective, observational analysis of banked, remnant serum samples submitted to the laboratory of a large, multi-hospital healthcare system. Samples were submitted over a 12-month period for the explicit purpose of testing for suspected EG ingestion. All samples underwent GC and the GDH-based assay.
Results
Of the 118 analyzed samples, 88 had no EG detected by GC, and 30 were “positive.” At the manufacturer’s threshold of 6 mg/dL EG, there was 100% (95%CI; 88.7–100) positive percent agreement (PPA) and 98% (92.1-99.6) negative percent agreement (NPA). Adjusted to a threshold of 9 mg/dL, both the PPA and NPA were 100%. Deming regression of the observed concentrations revealed a slope of 1.16 (1.01 to 1.32) and intercept of −5.3 (−8.9 to −1.7).
Conclusions
The GDH assay provides a sensitive and specific method for the detection and quantification of EG that is comparable to a GC-based method. More widespread use of this rapid, inexpensive assay could improve the care of patients with suspected toxic alcohol exposure. Further study is needed to evaluate the test performance in real-time patient treatment decisions.
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References
Kraut JA, Mullins ME. Toxic alcohols. N Engl J Med. 2018;378(3):270–80. https://doi.org/10.1056/NEJMra1615295.
Gummin DD, Mowry JB, Beuhler MC, Spyker DA, Rivers LJ, Feldman R, Brown K, Nathaniel PTP, Bronstein AC, Weber JA. 2021 Annual Report of the National Poison Data System© (NPDS) from America’s Poison Centers: 39th Annual Report. Clin Toxicol. 2022;60(12):1381–643. https://doi.org/10.1080/15563650.2022.2132768.
Wu AHB, McKay C, Broussard LA, Hoffman RS, Kwong TC, Moyer TP, Otten EM, Welch SL, Wax P. National Academy of Clinical Biochemistry laboratory medicine practice guidelines: recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department. Clin Chem. 2003;49(3):357–79. https://doi.org/10.1373/49.3.357.
McQuade DJ, Dargan PI, Wood DM. Challenges in the diagnosis of ethylene glycol poisoning. Ann Clin Biochem. 2014;51(Pt 2):167–78. https://doi.org/10.1177/0004563213506697.
Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol. 2008;3(1):208–25. https://doi.org/10.2215/CJN.03220807.
Beaulieu J, Roberts DM, Gosselin S, Hoffman RS, Lavergne V, Hovda KE, Megarbane B, Lung D, Thanacoody R, Ghannoum M. Treating ethylene glycol poisoning with alcohol dehydrogenase inhibition, but without extracorporeal treatments: a systematic review. Clin Toxicol. 2022;60(7):784–97. https://doi.org/10.1080/15563650.2022.2049810.
Kraut JA, **ng SX. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis. Am J Kidney Dis. 2011;58(3):480–4. https://doi.org/10.1053/j.ajkd.2011.05.018.
Soghoian S, Sinert R, Wiener SW, Hoffman RS. Ethylene glycol toxicity presenting with non-anion gap metabolic acidosis. Basic Clin Pharmacol Toxicol. 2009;104(1):22–6. https://doi.org/10.1111/j.1742-7843.2008.00334.x.
Heckerling PS. Ethylene glycol poisoning with a normal anion gap due to occult bromide intoxication. Ann Emerg Med. 1987;16(12):1384–6. https://doi.org/10.1016/s0196-0644(87)80426-2.
Ammar KA, Heckerling PS. Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap. Am J Kidney Dis. 1996;27(1):130–3. https://doi.org/10.1016/s0272-6386(96)90040-2.
Krasowski MD, Wilcoxon RM, Miron J. A retrospective analysis of glycol and toxic alcohol ingestion: utility of anion and osmolal gaps. BMC Clin Pathol. 2012;12:1. https://doi.org/10.1186/1472-6890-12-1.
Shaikh G, Sehgal R, Sandhu S, Vaddineni S, Fogel J, Rubinstein S. Changes in osmol gap in chronic kidney disease: an exploratory study. Ren Fail. 2014;36(2):198–201. https://doi.org/10.3109/0886022X.2013.838052.
Ahmed M, Janikowski C, Huda S, Ahmad A, Morrow L. Ethylene glycol poisoning with a near-normal osmolal gap: a diagnostic challenge. Cureus. 2020;12:e11937. https://doi.org/10.7759/cureus.11937.
Arora A. The ‘gap’ in the ‘plasma osmolar gap’. BMJ Case Rep. 2013;2013:bcr2013200250. https://doi.org/10.1136/bcr-2013-200250.
Steinhart B. Case report: severe ethylene glycol intoxication with normal osmolal gap--“a chilling thought”. J Emerg Med. 1990;8(5):583–5. https://doi.org/10.1016/0736-4679(90)90454-4.
Glaser DS. Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol ingestion. Ann Emerg Med. 1996;27(3):343–6. https://doi.org/10.1016/s0196-0644(96)70271-8.
Sagar AS, Jimenez CA, Mckelvy BJ. Lactate gap as a tool in identifying ethylene glycol poisoning. BMJ Case Rep. 2018;2018:bcr2018224243. https://doi.org/10.1136/bcr-2018-224243.
Pernet P, Bénéteau-Burnat B, Vaubourdolle M, Maury E, Offenstadt G. False elevation of blood lactate reveals ethylene glycol poisoning. Am J Emerg Med. 2009;27(1):132.e1–2. https://doi.org/10.1016/j.ajem.2008.04.029.
Brindley PG, Butler MS, Cembrowski G, Brindley DN. Falsely elevated point-of-care lactate measurement after ingestion of ethylene glycol. CMAJ. 2007;176(8):1097–9. https://doi.org/10.1503/cmaj.061288.
Hauvik LE, Varghese M, Nielsen EW. Lactate gap: a diagnostic support in severe metabolic acidosis of unknown origin. Case Rep Med. 2018;2018:5238240. https://doi.org/10.1155/2018/5238240.
Casavant MJ, Shah MN, Battels R. Does fluorescent urine indicate antifreeze ingestion by children? Pediatrics. 2001;107(1):113–4. https://doi.org/10.1542/peds.107.1.113.
Winter ML, Snodgrass WR. Urine fluorescence in ethylene glycol poisoning. N Engl J Med. 2007;356(19):2006. https://doi.org/10.1056/NEJMc070645.
Rosenstock JL, Joab TMJ, DeVita MV, Yang Y, Sharma PD, Bijol V. Oxalate nephropathy: a review. Clin Kidney J. 2021;15(2):194–204. https://doi.org/10.1093/ckj/sfab145.
Gaddam M, Velagapudi RK, Abu Sitta E, Kanzy A. Two gaps too many, three clues too few? Do elevated osmolal and anion gaps with crystalluria always mean ethylene glycol poisoning? BMJ Case Rep. 2017;2017:bcr2017221739. https://doi.org/10.1136/bcr-2017-221739.
Hansson P, Masson P. Simple enzymatic screening assay for ethylene glycol (ethane-1,2-diol) in serum. Clinica Chimica Acta. 1989;182(1):95–101. https://doi.org/10.1016/0009-8981(89)90153-8.
Juenke JM, Brown PI, McMillin GA, Johnson-Davis KL. Rapid and automated detection of ethylene glycol: suitable for hospital laboratories? Am J Clin Pathol. 2012;138(suppl 1):A139. https://doi.org/10.1093/ajcp/138.suppl1.125.
Juenke JM, Hardy L, McMillin GA, Horowitz GL. Rapid and specific quantification of ethylene glycol levels: adaptation of a commercial enzymatic assay to automated chemistry analyzers. Am J Clin Pathol. 2011;136(2):318–24.
Rooney SL, Ehlers A, Morris C, Drees D, Davis SR, Kulhavy J, Krasowski MD. Use of a rapid ethylene glycol assay: a 4-year retrospective study at an academic medical center. J Med Toxicol. 2016;12:172–9. https://doi.org/10.1007/s13181-015-0516-6.
Robson AF, Lawson AJ, Lewis L, Jones A, George S. Validation of a rapid, automated method for the measurement of ethylene glycol in human plasma. Ann Clin Biochem. 2017;54(4):481–9.
CLSI. Interference testing in clinical chemistry (CSLI document EP07), 3rd ed. 2018. Clinical and Laboratory Standards Institute; Wayne, PA.
CLSI. Assessment of equivalence or suitability of specimen types for medical laboratory measurement procedures (CSLI document EP35), 1st ed. 2019. Clinical and Laboratory Standards Institute; Wayne, PA.
CLSI. User verification of precision and estimation of bias; approved guideline (CSLI document EP15-A3), 3rd ed. 2014. Clinical and Laboratory Standards Institute; Wayne, PA.
Martin RF. General Deming regression for estimating systematic bias and its confidence interval in method-comparison studies. Clin Chem. 2000 Jan;46(1):100–4.
CLSI. Establishing and verifying an extended measuring interval through specimen dilution and spiking. In: CLSI guideline EP34. 1st ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med. 1999;340(11):832–8. https://doi.org/10.1056/NEJM199903183401102.
Jialal I, Devaraj S. Laboratory diagnosis of ethylene glycol poisoning: the cup is half full? Am J Clin Pathol. 2011;136(2):165–6. https://doi.org/10.1309/AJCPTZO0HRPKVPWM.
Blandford DE, Desjardins PR. A rapid method for measurement of ethylene glycol. Clin Biochem. 1994;27(1):25–30. https://doi.org/10.1016/0009-9120(94)90007-8.
Olson S, Gorodetsky R, Nacca N. Large false elevation in ethylene glycol in a patient with DKA [abstract]. Clin Tox. 2020;58(11):1075–280. https://doi.org/10.1080/15563650.2020.1804238.
Ghannoum M, Gosselin S, Hoffman RS, Lavergne V, Mégarbane B, Hassanian-Moghaddam H, Rif M, Kallab S, Bird S, Wood DM, Roberts DM, the EXTRIP Workgroup. Extracorporeal treatment for ethylene glycol poisoning: systematic review and recommendations from the EXTRIP workgroup. Crit Care., 56. 2023;27(1) https://doi.org/10.1186/s13054-022-04227-2.
Mégarbane B. Treatment of patients with ethylene glycol or methanol poisoning: focus on fomepizole. Open Access Emerg Med. 2010;24(2):67–75. https://doi.org/10.2147/OAEM.S5346.
Hovda KE, Gadeholt G, Evtodienko V, Jacobsen D. A novel bedside diagnostic test for methanol poisoning using dry chemistry for formate. Scand J Clin Lab Invest. 2015;75(7):610–4. https://doi.org/10.3109/00365513.2015.1066847.
Hovda KE, Lao YE, Gadeholt G, Jacobsen D. Formate test for bedside diagnosis of methanol poisoning. Basic Clin Pharmacol Toxicol. 2021;129(1):86–8. https://doi.org/10.1111/bcpt.13597.
Lao YE, Heyerdahl F, Jacobsen D, Hovda KE. An enzymatic assay with formate oxidase for point-of-care diagnosis of methanol poisoning. Basic Clin Pharmacol Toxicol. 2022;131(6):547–54. https://doi.org/10.1111/bcpt.13789.
Zakharov S, Kurcova I, Navratil T, Salek T, Komarc M, Pelclova D. Is the measurement of serum formate concentration useful in the diagnostics of acute methanol poisoning? A prospective study of 38 patients. Basic Clin Pharmacol Toxicol. 2015;116(5):445–51. https://doi.org/10.1111/bcpt.12338.
Osterloh JD, Pond SM, Grady S, Becker CE. Serum formate concentrations in methanol intoxication as a criterion for hemodialysis. Ann Intern Med. 1986;104(2):200–3. https://doi.org/10.7326/0003-4819-104-2-200.
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We thank David Templeton, MS, and Catachem Inc. for in-kind support in providing reagents.
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David Templeton, MS, and Catachem Inc. (Oxford, CT) provided the glycerol dehydrogenase reagents. Neither Mr. Templeton nor any other agents or employees of Catachem Inc. had any role in the study design or the data analysis.
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Data in this study were previously presented at North American Congress of Clinical Toxicology (NACCT), San Francisco, CA, 2022.
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Filip, A.B., Farnsworth, C.W., Mullins, M.E. et al. Accuracy of a Glycerol Dehydrogenase Assay for Ethylene Glycol Detection. J. Med. Toxicol. 19, 362–367 (2023). https://doi.org/10.1007/s13181-023-00967-x
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DOI: https://doi.org/10.1007/s13181-023-00967-x