Ethylene Glycol Poisoning. The Value of Glycolic Acid Determinations for Diagnosis and Treatment

Hewlett, Tracy P.; McMartin, Kenneth E.; Lauro, Alert J.; Ragan, Francis Avery

doi:10.3109/15563658608992602

Cited by 61 publications

(20 citation statements)

References 11 publications

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“…Diagnosis of ethylene glycol poisoning can be difficult because few institutions have timely access to direct measurement of the compound in blood or the urine [76]. Hence, it is necessary to rely on other biochemical clues to the diagnosis and to have a high index of suspicion in patients presenting with suggestive symptoms and signs.…”

Section: Lactate Measurement In Ethylene Glycol Poisoningmentioning

confidence: 99%

Lactic acidosis: an update

Seheult

Fitzpatrick

Boran

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

100

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Lactate is one of the most crucial intermediates in carbohydrate and nonessential amino acid metabolism. The complexity of cellular interactions and metabolism means that lactate can be considered a waste product for one cell but a useful substrate for another. The presence of elevated lactate levels in critically ill patients has important implications for morbidity and mortality. In this review, we provide a brief outline of the metabolism of lactate, the pathophysiology of lactic acidosis, the clinical significance of D-lactate, the role of lactate measurement in acutely ill patients, the methods used to measure lactate in blood or plasma and some of the methodological issues related to interferences in these assays, especially in the case of ethylene glycol poisoning.

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Section: Lactate Measurement In Ethylene Glycol Poisoningmentioning

confidence: 99%

Lactic acidosis: an update

Seheult

Fitzpatrick

Boran

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

100

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“…Selected methods for EG and glycolic acid are summarized in Tables 1 and 2, respectively. The presently preferred method for determination of EG by GC is based on phenylboronation (Hewlett et al 1986;Porter and Auansakul 1982). When the analysis is performed with a commonly used capillary column, it appears to be free from known interferences (Porter et al 1994).…”

Section: Methodsmentioning

confidence: 99%

“…Because of its rapid metabolism EG may be low or undetectable in plasma/serum while GA attains high levels (Fraser and MacNeil 1993;Hewlett et al 1986). The elimination half-life of EG is increased more than tenfold in the presence of ethanol because both compounds compete for the active site of alcohol dehydrogenase (Eder et al 1998;Jacobsen et al 1988).…”

Section: Toxicokinetics and Metabolism Of Ethylene Glycolmentioning

confidence: 99%

“…Because of the high capacity of alcohol dehydrogenase to oxidize EG in the absence of a competitive inhibitor the measurement of GA in addition to that of EG is important for diagnosis and therapy of intoxication. In fact the serum concentration of GA has been shown to be correlated more closely with the clinical symptoms than the concentration of EG (Hewlett et al 1986). …”

Section: Toxicokinetics and Metabolism Of Ethylene Glycolmentioning

confidence: 99%

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Ethylene glycol: an estimate of tolerable levels of exposure based on a review of animal and human data

2004

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Upon ingestion ethylene glycol (EG, monoethylene glycol) is rapidly absorbed from the gastrointestinal tract, and depending on the severity of exposure signs of toxicity may progress through three stages. Neurological effects characterize the first step consisting of central nervous depression (intoxication, lethargy, seizures, and coma). The second stage, usually 12-24 h after ingestion, is characterized by metabolic acidosis due to the accumulation of acidic metabolites of EG, primarily glycolic acid (GA), contributing to the ensuing osmolal and anion gaps. Stage 3, generally 24-72 h after ingestion, is determined mainly by oxalic acid excretion, nephropathy, and eventual renal failure. Because the toxicity of EG is mediated principally through its metabolites, adequate analytical methods are essential to provide the information necessary for diagnosis and therapeutic management. The severe metabolic acidosis and multiple organ failure caused by ingestion of high doses of EG is a medical emergency that usually requires immediate measures to support respiration, correct the electrolyte imbalance, and initiate hemodialysis. Since metabolic acidosis is not specific to EG, whenever EG intoxication is suspected, every effort should be made to determine EG as well as its major metabolite GA in plasma to confirm the diagnosis and to institute special treatment without delay. A number of specific and sensitive analytical methods (GC, GC-MS, or HPLC) are available for this purpose. Due to the rapid metabolism of EG, the plasma concentration of GA may be higher than that of EG already upon admission. As toxicity is largely a consequence of metabolism of EG to GA and oxalic acid, the simultaneous quantification of EG and GA is important. Formation of calcium oxalate monohydrate in the urine may be a useful indicator of developing oxalate nephrosis although urine crystals can result without renal injury. The pathways involved in the metabolism of EG are qualitatively similar in humans and laboratory animals, although quantitative differences have been reported. Comparison between species is difficult, however, because the information on humans is derived mainly from acute poisoning cases whereas the effects of repeated exposures have been investigated in animal experiments. Based on published data the minimum human lethal dose of EG has been estimated at approx. 100 ml for a 70-kg adult or 1.6 g/kg body weight (calculation of dose in ml/kg to mg/kg based in EG density=1.11 g/l). However, human data from case reports are generally insufficient for the determination of a clear dose-response relationship and quantification of threshold doses for systemic toxicity, in particular renal effects, is limited. As toxicity is largely a consequence of metabolism of EG to GA, it is important to note that no signs of renal injury have developed at initial plasma glycolate concentrations of up to 10.1 mM (76.7 mg/dl). Plasma EG levels of 3.2 mM (20 mg/dl) are considered the threshold of toxicity for systemic exposure, if thera...

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“…Two rapid oxidations, fi rst to glycoaldehyde (by alcohol dehydrogenase) and then to glycolic acid (by aldehyde dehydrogenase) are followed by the relatively slow oxidation to glyoxylic acid, leading to buildup of metabolite glycolic acid. 4 The presence of large amounts of glycolic acid leads to anion gap metabolic acidosis usually within 12 to 24 hours of ingestion of EG. Symptoms in this stage can range from hypotension and tachypnea to frank cardiopulmonary collapse with pulmonary edema and multiorgan failure.…”

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confidence: 99%

Kidney‐pancreas transplantation in the setting of donor ethylene glycol poisoning

Barbas

Sweeney

Collins

et al. 2010

Dialysis & Transplantation

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T he safety of kidney or kidneypancreas transplantation in the setting of donor ethylene glycol (EG) poisoning has not been well established. While renal transplantation has been reported from a donor after EG toxicity, 1 there are no reports of successful simultaneous pancreas-kidney (SPK) transplantation in this setting in the literature. This article describes a case of successful kidney-pancreas transplantation in the setting of donor death from EG. Ethylene glycol is an odorless, colorless alcohol with a sweet taste used as antifreeze for automotives. Ingestion may be accidental, most commonly affecting children and household pets, or may be associated with attempted suicide. Approximately 5,000 people in the United States are treated for EG poisoning per year, with about 30 to 40 resulting in fatalities. 2 The hallmarks of EG poisoning are central nervous system (CNS) depression, profound metabolic acidosis, cardiopulmonary compromise, and acute renal failure.Ethylene glycol has 3 primary toxic effects, that are most easily classifi ed by their differing time courses (Figure 1). The fi rst stage runs from 30 minutes to 12 hours after ingestion and is marked by CNS depression and gastritis by the unmetabolized EG, an effect similar to ethanol intoxication. 3 Central nervous system symptoms of intoxication with lethargy, seizures, and coma predominate during this initial stage. The second stage takes over as EG is metabolized in the liver. Two rapid oxidations, fi rst to glycoaldehyde (by alcohol dehydrogenase) and then to glycolic acid (by aldehyde dehydrogenase) are followed by the relatively slow oxidation to glyoxylic acid, leading to buildup of metabolite glycolic acid. 4 The presence of large amounts of glycolic acid leads to anion gap metabolic acidosis usually within 12 to 24 hours of ingestion of EG. Symptoms in this stage can range from hypotension and tachypnea to frank cardiopulmonary collapse with pulmonary edema and multiorgan failure. 5 The third stage of EG toxicity involves renal failure, usually appearing about 24 to 72 hours after ingestion. The metabolite glyoxylic acid can be converted to up to 4 different metabolites, depending on the relative presence of co-metabolites. The metabolites are: glycine (relatively nontoxic, formed in the presence of pyridoxine), alpha-hydroxy-beta-ketoadipate (formed in the presence of thiamine), formic acid (not usually present in large amounts), and oxalate. 6 Oxalate binds serum calcium ions to form the compound calcium oxalate, that precipitates in crystalline form. Not only does this have the capacity of causing hypocalcemia, possibly leading to tetany and prolonged QTc, but can also result in the deposition of the crystals in the renal cortex. 7 These insoluble calcium-oxalate crystals are deposited in the proximal convoluted tubule and interstitium, causing physical trauma to cells, obstructing the tubule, and inciting an infl ammatory reaction. Ultimately, these mechanisms lead to necrosis of the proximal tubule. This mechanism of acute renal failu...

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Ethylene Glycol Poisoning. The Value of Glycolic Acid Determinations for Diagnosis and Treatment

Cited by 61 publications

References 11 publications

Lactic acidosis: an update

Lactic acidosis: an update

Ethylene glycol: an estimate of tolerable levels of exposure based on a review of animal and human data

Kidney‐pancreas transplantation in the setting of donor ethylene glycol poisoning

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