Abstract
Severe metabolic acidosis with increased anion gap may be due to ethylene glycol poisoning. Two methods are available to quantify ethylene glycol in serum: the first non-specific method by spectrophotometry used for screening and the second one by gas chromatography coupled to mass-spectrometry used for confirmation. Nevertheless, gas chromatography is not available everywhere and requires technical expertise, challenging the definitive diagnosis of ethylene glycol poisoning in the emergency department (ED). The cross reaction between the enzyme L-lactate oxidase, used for the determination of lactate by many blood gas analyzers, and ethylene glycol metabolites (glycolate and oxalate) is now well known.1Manini A.F. Hoffman R.S. McMartin K.E. et al.Relationship between serum glycolate and falsely elevated lactate in severe ethylene glycol poisoning.J Anal Tox. 2009; 33: 174-176Crossref PubMed Scopus (36) Google Scholar Futhermore, similarities in chemical structure exist between ethylene glycol and lactate and could alter the detection of ethylene glycol by spectrophotometry. Indeed, the enzymatic determination of ethylene glycol in serum uses glycerol dehydrogenase to oxidize ethylene glycol with concomitant production of nicotinamide adenine dinucleotide, which is detected by spectrophotometry. In critically ill patients with increased serum lactate, oxidation of lactate to pyruvate catalyzed by L-lactate dehydrogenase increases the production of nicotinamide adenine dinucleotide, which may cross-react with the ethylene glycol assay, causing false elevation of ethylene glycol.2Eder A.F. McGrath C.M. Dowdy Y.G. et al.Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis.Clin Chem. 1998; 44: 168-177PubMed Google Scholar We report the case of a 58-year-old diabetic man who presented to the ED with abdominal pain. On admission, he had an arterial pH of 6.65, an increased anion gap (43 mEq/L), and a serum lactate concentration of 36 mmol/L. A spectrophotometric assay (PerkinElmer Lambda 25 UV/VIS, Waltham, MA) indicated an elevated serum ethylene glycol concentration (46.5 mg/dL). Salicylate and alcohol were not detectable. Urinalysis revealed ketones at 4 mmol/L. Abdominal computed tomography (CT) scan was normal. The patient developed hemodynamic shock (blood pressure was not measurable and heart rate was 140/min) associated with acute renal failure and he received intravenous fomepizole for presumed ethylene glycol poisoning. Intriguingly, serial serum ethylene glycol concentration assessed by spectrophotometry were steady (44 mg/dL) and arterial lactate (ABL 825, Radiometer, Copenhagen, Denmark) concentration remained elevated (25 mmol/L) despite continuous veno-venous hemodiafiltration for 20 hours.3Megarbane B. Borron S.W. Baud F.J. Current recommendations for treatment of severe toxic alcohol poisonings.Intensive Care Med. 2005; 31: 189-195Crossref PubMed Scopus (126) Google Scholar Finally, severe lactic acidosis was likely related to a plasma metformin concentration of 8.60 mg/L (normal 0−1.34) revealed by high-performance liquid chromatography (Beckmann, Fullerton, CA). The persistent elevation of serum lactate interfering with the screening assay for ethylene glycol probably explains why blood ethylene glycol concentration remained steady despite renal replacement therapy. The second report concerns a 86-year-old man who presented to the ED with hypotension, coma, and abdominal tenderness and guarding on palpation. He had ketoacidosis (arterial pH 7.09 and urine ketone 8 mmol/L), increased anion gap (20 mEq/L) and normal arterial blood lactate assessed at admission and before any therapeutic intervention. A false elevation of blood ethylene glycol concentration (33.5 mg/dL) determined by spectrophotometry (PerkinElmer) was confirmed by its absence using gas chromatography/mass-spectrometry (Carlo Erba, Val de Rueil, France). Abdominal CT scan revealed necrotic pancreatitis. As suggested by this case, ketone bodies could also interfere with the spectrophotometric assay because β-hydroxybutyrate (which was not specifically measured in this patient) and ethylene glycol share a similar molecular structure.4Van Hee P. Neels H. De Doncker M. et al.Analysis of gamma-hydroxybutyric acid, DL-lactic acid, glycolic acid, ethylene glycol and other glycols in body fluids by a direct injection gas chromatography-mass spectrometry assay for wide use.Clin Chem Lab Med. 2004; 42: 1341-1345Crossref PubMed Scopus (35) Google Scholar Our observations suggest that determination of ethylene glycol concentrations in serum by spectrophotometry may be inaccurate in the presence of substantially elevated serum lactate or ketoacid concentrations. Nevertheless, structural similarity is probably not the exclusive factor involved in this analytical interference since other substances that shift the redox state to favor nicotinamide adenine dinucleotide may possibly cause this error. Further analytical studies are needed to confirm our hypothesis. Interferences in the screening test for ethylene glycol could lead to misdiagnosis resulting in inappropriate and costly therapies. Practitioners should be made aware of this possibility and should discern what assay is used by their local laboratory for ethylene glycol determination.
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