Lactate gap in ethylene glycol toxicity

From Brindley P.G et al., CMAJ 4-10-07, 176(8) pg1097-1099

When making a decision about urgent dialysis it is important to have an much information as quickly as possible. In suspected ethylene glycol toxicity time is of the essence. Waiting 3-4 hours or more for the ethylene glycol level to come back can be deleterious to the patient. Often times we are left to make the decision to begin dialysis or therapy based upon a high degree of suspicion from the available laboratory data and patient circumstances. During conference recently I heard of another pearl that could help in determining if ethylene glycol was ingested.

This is termed the lactate gap. Essentially this is the difference in values obtained from 2 different analyzer methods. As seen in the graph, taken from this paper, the commonly used Radiometer method can result in a falsely elevated lactate level when compared to other assays (iSTAT, Bayer, Vtros and Beckman).

Why is this the case?

This likely occurs because metabolites of ethylene glycol cross react with L-lactate oxidase. The Radiometer assay uses the enzyme L-lactate oxidase to accelerate the reaction between L-lactate and oxygen, the products of the reaction being hydrogen peroxide and pyruvate (click here for discussion of this). The L-lactate concentration is then computed from the measured hydrogen peroxide concentration. It is thought that glycolate (a metabolite of ethylene glycol) is able to interact with L-lactate oxidase and produces a significant amount of hydrogen peroxide and thus the test reports as a high lactate level.

The enzymatic L-lactate assay are also subject to interference from certain drugs at toxic levels such as; Isoniazid, Acetaminophen and Thiocyanate.

The radiometer method of detecting lactate is commonly used in point-of-care testing such as those reported by ABG's. It is important to know what your lab is using when interpreting lactate values. Serum lactate levels are typically computed using a non-radiometry method.

Obtaining simultaneous radiometer lactate and another method of lactate measurement and computing the lactate gap (the difference between the two values) can help in distinguishing true lactic acidosis from ethylene glycol toxicity.