Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Ethylene Glycol and Propylene Glycol Toxicity
What Laboratory Tests Can Help In Evaluating Patients Exposed to Ethylene Glycol?

Learning Objectives

Upon completion of this section, you should be able to

• identify the abnormal laboratory findings associated with ethylene glycol poisoning and
• list three measurements that can assist with diagnosis of ethylene glycol poisoning.

Introduction

All patients with known or suspected ethylene glycol ingestion require the following tests

• arterial blood gases
• blood glucose
• serum electrolytes
• blood ethanol

Other helpful laboratory tests may include

• serum BUN and creatinine
• calcium and magnesium levels
• acetaminophen and aspirin levels
• liver function tests
• urinalysis (with special attention to crystalluria)

A measured osmolality by the freezing point depression method is needed to detect an osmolal gap. Results of these laboratory tests will confirm the presence and degree of metabolic acidosis and allow calculation of the anion and osmolal gaps (Figure 2).

Ethanol, Methanol, Ketoacidosis

A blood ethanol level will establish whether initial CNS symptoms may be due to ethanol. The presence of ethanol will also have a substantial impact on metabolism and therapy. Patients who have both anion and osmolal gap should also have blood methanol tests. Serum lactate and betahydroxybutyrate levels may be indicated for an alcoholic patient, if alcoholic ketoacidosis is suspected (Meditext 2004).

Urinary Crystals

The presence of calcium oxalate or hippurate crystals in the urine, together with an elevated anion gap or osmolal gap, strongly suggests ethylene glycol poisoning (Albertson 1999). Urinary crystals result from

• the precipitation of calcium by the oxalic acid metabolite of ethylene glycol
• the reaction of the glycine metabolite with benzoic acid, which forms hippuric acid

Urinary crystals can take many forms

• dumbbells
• envelopes
• needles (most commonly) (Jacobsen, Hewlett et al. 1988)

Absence of urinary crystals, however, does not rule out poisoning. Numerous studies have documented that renal damage occurs after ethylene glycol ingestion without deposition of calcium oxalate crystals in the kidney (Vale 1979; Hall AH 1992).

Urine Fluorescence

Because some antifreeze products contain fluorescein, the urine may fluoresce under a Wood’s lamp (Winter, Ellis et al. 1990). However, recent studies argued if Wood’s lamp determination of urine fluorescence could be a reliable diagnostic test (Casavant, Shah et al. 2001; Wallace, Suchard et al. 2001; Sharma, O'Shaughnessy et al. 2002).

Serum Analysis

An elevated serum level of ethylene glycol confirms ethylene glycol poisoning. Significant toxicity is often associated with levels greater than 25 milligrams per deciliter (mg/dL) (Hall AH 1992; Goldfrank LR 1998).

False Positives

Communication with the laboratory is critical in poisoning cases for several reasons.

• 2,3-butanediol, often found in the plasma of alcoholics, can be mistakenly identified as ethylene glycol when the analysis is performed by gas chromatography (Jones, Nilsson et al. 1991).
• Propylene glycol can also interfere with some ethylene glycol assays (Robinson, Scott et al. 1983; Apple, Googins et al. 1993; Hilliard, Robinson et al. 2004).
• An inherited metabolic disorder can present as ethylene glycol intoxication from laboratory results (Pien, van Vlem et al. 2002).

Glycolic Acid Analysis

Recent studies have demonstrated usefulness of glycolic acid analysis in ethylene glycol poisoning cases (Fraser 1998; Porter, Rutter et al. 2001; Fraser 2002). Most laboratories routinely screen for unchanged ethylene glycol in suspected poisonings. They estimate the amount of ethylene glycol present in positive cases even though toxicity from ethylene glycol exposure is primarily caused by one metabolite—glycolic acid. Measuring glycolic acid in ethylene glycol poisonings has certain advantages

• findings correlate better with ethylene glycol toxicity than ethylene glycol levels
• findings determine how much ethylene glycol has metabolized to glycolic acid
• the presence of glycolic acid objectively indicates toxicity
• the test confirms that the metabolic acidosis was due to ethylene glycol poisoning rather than another cause (Fraser 2002)

Yao and Porter (1996) were the first to develop a procedure for simultaneously determining ethylene glycol and its major toxic metabolite, glycolic acid. Porter and colleagues published a modification of the method a few years later. (Yao and Porter 1996; Porter, Rutter et al. 1999)

Anion and Osmolal Gaps

The presence of metabolic acidosis with both anion and osmolal gaps is an important clue to the diagnosis (Friedman, Greenberg et al. 1962; Parry and Wallach 1974; Szerlip 1999). Numerous toxic substances are associated with an elevated anion gap (Table 2) (Goldfrank LR 1990). An elevated osmolal gap suggests the presence of a low-molecular weight substance.

Only four significant conditions will cause metabolic acidosis and elevate both the anion and osmolal gaps

1. methanol poisoning
2. ethylene glycol poisoning
3. alcoholic ketoacidosis
4. diabetic ketoacidosis

Acetone causes an osmolal gap. Lactic acidosis or propylene glycol intoxication also is capable of causing metabolic acidosis with osmolal gap.

However, when large quantities of ethanol and ethylene glycol are ingested concurrently, metabolic acidosis may be inhibited or delayed. In such cases, the patient may initially develop an osmolal gap but will not immediately develop acidosis or an anion gap.

Although an osmolal gap is often cited as indirect evidence of the presence of an exogenous alcohol or glycol, other substances or conditions may be causative. Conversely, failure to find an osmolal gap may lead to the erroneous assumption that no exogenous substances are present. A small osmolal gap may, however, represent a significant alcohol level.

Caution must be used when interpreting the osmolal gap. Recent reviews argued that the use of the osmolal gap as a screening tool for ethylene glycol has significant limitations and remains hypothetical (Glaser 1996; Koga, Purssell et al. 2004; Purssell, Lynd et al. 2004).

Key Points

• Ethylene glycol poisoning is strongly suggested by
  • an elevated anion-gap metabolic acidosis
  • an elevated osmolal gap
  • urinary crystals
• Measurement of serum ethylene glycol levels can confirm poisoning.

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