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Journal Scan

March 2019

Increase in blood lipids causes falsely low bicarbonate results

Summarized from Stein H. Spuriously low serum bicarbonate in patients with hyperlipidemia: a report of 4 cases. Am J Kidney Disease 2018. Published online ahead of print June 28th 2018. Available at:
Arterial blood gas (ABG) analysis allows full assessment of patient acid-base status predominantly via the following three parameters generated during the analysis: arterial blood pH; partial pressure of carbon dioxide in arterial blood pCO2(a); and concentration of bicarbonate (HCO3) in arterial blood. Two of these parameters, pH and pCO2, are measured directly by electrodes contained within the blood gas analyzer, but bicarbonate is derived by calculation from the two measured parameters using a modified form of the Henderson-Hasselbalch equation that relates all three parameters. 

A more partial assessment of patient acid-base status is provided for by the inclusion of serum bicarbonate in the general routine biochemical profile of venous blood performed by high-throughput analyzers in the central laboratory. In this case bicarbonate is measured directly, usually by an enzymatic/photometric method that, strictly speaking, measures serum total carbon dioxide (tCO2) concentration. Nomenclature of bicarbonate for the assay is justified on the grounds that bicarbonate constitutes ∼98 % of tCO2.

In general, there is good (clinically acceptable) concordance between calculated bicarbonate generated during blood gas analysis and measured bicarbonate (tCO2) generated by central laboratory analyzers; concentrations are usually within 1-3 mmol/L (mEq/L) of each other (approximate reference interval for bicarbonate: 22-28 mmol/L (mEq/L).

As this recently published case study report makes clear, marked discordance between the two bicarbonate values can occur. Consequent conflicting evidence of an acid-base disturbance allows the potential for inaccurate diagnosis and inappropriate treatment. 

The author of this report describes four very similar cases of discordant bicarbonate results occurring in one US hospital during the past year. In all four cases bicarbonate discordance could be attributed to interference of severe hyperlipidemia in the enzymatic bicarbonate assay used in the central laboratory at the author’s hospital. The turbidimetric-associated interference results in artefactual marked reduction in serum bicarbonate concentration. 

The measured serum bicarbonate concentrations of the four patients were respectively: 8 mEq/L (mmol/L); <5 mEq/L (mmol/L); 6 mEq/L (mmol/L); and 12 mEq/L (mmol/L). Since these results are indicative of moderate to severe acidosis, they prompted immediate (within 1 hour) arterial blood gas analysis to fully assess acid-base status of the four patients. The calculated bicarbonate concentrations of the four patients derived from blood gas analysis were respectively: 22.8 mEq/L (mmol/L); 22 mEq/L (mmol/L); 21.5 mEq/L (mmol/L); and 18.1 mEq/L (mmol/L).

In all cases of calculated bicarbonate and measured pH, pCO2(a) indicated either normal acid-base status or slight acidosis. Instead of the usual 1-3 mEq/L (mmol/L) discordance between measured and calculated bicarbonate, in these four patients, discordance ranged from 6.1 to 17 mEq/L (mmol/L).

All four patients had profound hyperlipidemia, with serum triglyceride concentration ranging from 3,600 mg/dL (41 mmol/L) to 5,680 mg/dL (64 mmol/L). (Optimum reference interval 0-150 mg/dL; 0-1.7 mmol/L). Confirmatory evidence that hyperlipidemia is the cause of spuriously low measured bicarbonate values depends on measuring bicarbonate before and after sample ultracentrifugation, a process that clears serum of lipids. The author reports that ultracentrifugation of a sample from one of the four study patients reduced bicarbonate discrepancy from 17 mEq/L to just 4 mEq/L. 

In discussion of these four cases the author highlights other case history reports of marked discordance between measured and calculated bicarbonate, and reveals a consensus that a cut-off serum triglyceride >1000mg/dL (11.3 mmol/L) is associated with artefactual decrease in measured bicarbonate that should prompt ultracentrifugation of samples or addition of a lipid-clearing agent to the sample prior to bicarbonate measurement.

He also makes the important point that severe hyperlipidemia only affects enzymatic bicarbonate (tCO2) assays; alternative, currently less available, indirect ion-specific electrode bicarbonate (tCO2) assays are unaffected by hyperlipidemia.  

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Chris Higgins

has a master's degree in medical biochemistry and he has twenty years experience of work in clinical laboratories.

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