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Technical Briefs |
1
Lexington VA Hospital, Lexington, KY 40536
2
Department of Pathology and Laboratory Medicine, University
a author
for correspondence: fax 606-257-8932, e-mail wporter{at}pop.uky.edu
In the differential evaluation of patients with high anion gap metabolic acidosis of unknown origin, lactate determinations are frequently performed. For patients who ingest ethylene glycol (present in antifreeze), the high anion gap metabolic acidosis is the result of the metabolism of ethylene glycol to glycolic acid (1)(2).
We encountered unusual lactate results, when measured on the Beckman LX 20 (Beckman Coulter), for two patients who had ingested ethylene glycol. Specifically, the lactate results were suppressed (i.e., no result) with an appended error message, "rate high". When these specimens were diluted threefold, measurable lactate values were obtained.
The Beckman lactate method is based on a lactate oxidase/peroxidase
coupled reaction with endpoint determination. The lactate concentration
is determined from the absorbance (A) measurement taken
after reaction equilibrium has been established. To ensure an
equilibrium steady state, a rate measurement is made during the
expected steady-state portion of the measurement period. A reaction
rate 
10 mA/min would indicate a nonequilibrium reaction
condition and would lead to suppressed results and a "rate high"
error flag.
We suspected, based on their structural similarities, that glycolate reacted as a poor substrate for lactate oxidase, generating a reaction rate >10 mA/min during the expected steady-state portion of the lactate reaction and thus causing the "rate high" error flag. To investigate this possibility, aqueous solutions with glycolic acid concentrations of 0–26.3 mmol/L were assayed for lactate on the Beckman LX 20 and on the Vitros 950 (Johnson & Johnson).
When measured by LX 20, glycolate concentrations up to 11.8 mmol/L
produced an apparent lactate value up to 0.4 mmol/L, whereas glycolate
concentrations 13.2 mmol/L produced a suppressed lactate result and a
"rate high" flag (Table 1
). Specimens with a "rate high" flag indeed displayed
reaction rates >10 mA/min. Fig. 1
depicts the reaction course for lactate, glycolic acid, and
combined lactate/glycolic acid. The equilibrium state for lactate after
100 s and the nonequilibrium reaction rate for glycolic acid
are clearly apparent. The vertical lines mark the time period during
which the reactions rate measurements were made.
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When measured by the Vitros lactate method, all specimens with glycolic acid concentrations of 0–26.3 mmol/L registered zero lactate values. The Vitros lactate method is also based on a lactate oxidase/peroxidase coupled reaction. However, reaction conditions are obviously sufficiently different to avoid glycolic acid interference.
Values of zero were obtained when aqueous solutions with ethylene glycol concentrations up to 80.7 mmol/L (500 mg/dL) were assayed for lactate by the Beckman LX 20 method.
In ethylene glycol poisoning, the concentration of glycolic acid in
serum correlates more closely with clinical severity than does that for
ethylene glycol (3). For this reason, our laboratory
developed gas chromatography-flame ionization (4) and gas
chromatography-mass spectrometry (5) methods for the
simultaneous determination of ethylene glycol and glycolic acid in
serum. A rapid, nonchromatographic measure of glycolic acid would be of
value for those laboratories without gas chromatographic
instruments. We thus explored the possibility of using the Beckman
lactate oxidase-based reaction for a kinetic measure of glycolic acid
concentration. Whereas the reaction rate for glycolic acid is a
reasonably linear function of its concentration between 3.3 and 26.3
mmol/L (Table 1
and Fig. 1
), it becomes curvilinear between 26.3 and
52.6 mmol/L (data not shown). Moreover, the slope of the reaction rate
vs glycolic acid concentration response curve is inversely related to
the lactate concentration. Thus, application of this kinetic
method as a measure of glycolic acid concentration in known cases of
ethylene glycol ingestion cannot be recommended. An enzymatic assay for
glycolic acid, based on a glycolate oxidase/peroxidase coupled
reaction, has been reported (6). Lactate interferes;
therefore, the glycolic acid response must be corrected for the
contribution of endogenous lactate.
We measured serum ethylene glycol and glycolic acid concentrations for
a series of 35 cases of ethylene glycol ingestion. Initial values for
ethylene glycol and glycolic acid were 0.97–130.6 mmol/L (6–810
mg/dL) and 0–38 mmol/L, respectively. As reported previously
(3)(5), ethylene glycol concentrations correlate
poorly with those for glycolic acid in ethylene glycol intoxication.
For 16 patients, the initial glycolic acid concentration was >13
mmol/L [with corresponding ethylene glycol concentrations of
0.97–121.9 mmol/L (6–756 mg/dL)] and, based on the data in Table 1
,
would have produced a "rate high" flag if their sera were also
measured for lactate on the Beckman LX 20. Thus, laboratories using the
Beckman Synchron lactate method should be alert to the
possibility of glycolic acid as the cause of a "rate high" error
flag. This information could be an important clue to the possibility of
ethylene glycol ingestion as the cause of an otherwise unknown high
anion gap metabolic acidosis. Indeed, this scenario occurred in our
institution. These laboratories should also be aware of the
modest overestimation of lactate caused by glycolic acid when present
at concentrations <13 mmol/L.
Footnotes
2>of Kentucky Medical Center, Lexington, KY 40536
References
The following articles in journals at HighWire Press have cited this article:
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  P. G. Brindley, M. S. Butler, G. Cembrowski, and D. N. Brindley Falsely elevated point-of-care lactate measurement after ingestion of ethylene glycol Can. Med. Assoc. J., April 10, 2007; 176(8): 1097 - 1099. [Abstract] [Full Text] [PDF]
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