Lactate and the osmolar gap
===========================

* Manish M. Sood MD
* Robert Richardson MD

*   © 2007 Canadian Medical Association or its licensors

[The authors respond:]

We thank Frances Rosenberg for her comment on our paper.1 The contribution of lactic acid to the osmolar gap is complex. Lactic acid ionizes; Rosenberg astutely mentions that the cation accompanying lactate is sodium. Theoretically, therefore, an elevated lactate concentration should not elevate the osmolar gap because the osmolar gap calculation accounts for sodium. However, elevations in the osmolar gap with lactic acidosis and shock have been consistently reported in both human and animal studies.2–4

There are 3 likely explanations for these observations. First, many reports have described elevations in the osmolar gap in patients who have prolonged stays in the intensive care unit with sepsis or organ hypoperfusion. Medications such as lorazepam, multivitamin preparations and nitroglycerin are often stored in propylene glycol, a solvent that is known to increase the osmolar gap and lead to lactic acidosis.5 Second, in alcoholic patients without detectable serum ethanol levels, endogenous compounds such as glycerol, acetone and acetone's metabolic by-products have been shown to elevate the osmolar gap.6 If these patients have concurrent liver damage, a type 2 lactic acidosis may be present because the liver fails to clear lactate. These 2 examples illustrate situations in which an elevated osmolar gap and elevated lactate concentration may be detected concurrently; this may explain the confusion in the literature.

Lastly, in experimental settings, Schelling and colleagues found that the osmolar gap in a cohort of hospitalized patients with lactic acidosis was elevated (10.3 ± 2.0 mmol/kg) compared with that of control patients.2 It is felt that with lactic acidosis, cell breakdown leads to the release of other products of glycogen breakdown that contribute to the elevation of the osmolar gap. This contribution is relatively minor (generally leading to an osmolar gap of less than 25 mOsmol/kg), but it is detectable. Thus, we feel that an elevated lactate concentration does make a contribution to increasing the osmolar gap.

## Footnotes

*   **Competing interests:** None declared.

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