Biological variation of the osmolality and the osmolal gap

Abstract

The ingestion of toxic alcohols including methanol, ethylene glycol, and isopropanol remains a significant public health problem. These compounds can cause central nervous system depression and, for methanol and ethylene glycol, organ damage from toxic metabolites. The presence of these compounds in serum/plasma can often be determined and monitored by measuring the osmolal gap (OG). However, other compounds originating from endogenous or exogenous sources, such as propylene glycol and acetone, can also increase the OG. Conversion factors can be used to estimate specific concentrations of acetone and toxic alcohols from OG. In this retrospective study, data were analyzed for 260 samples originating from 158 unique patients that had determination of both OG and concentrations for toxic alcohols at an academic medical center central laboratory. Specific analysis included gas chromatography (acetone, isopropanol, methanol, ethylene glycol, propylene glycol) and/or enzymatic assay (ethylene glycol). Many samples also contained ethanol. The data was grouped by type of ingestion. The present study analyzed the relationship between the OG calculated from measured plasma/serum osmolality and the OG estimated by applying conversion factors to measured concentrations of the different compounds. The correlations tend to be linear and vary by compound, with methanol and ethylene glycol having the highest R2 values of 0.93 and 0.95, respectively, consistent with other published studies. Higher variability was seen for the data for isopropanol and acetone. For each of the data subsets, the estimated toxic alcohol concentration calculated using conversion factors from OG tends to overestimate the actual concentration of the compound. Overall, the present study demonstrates the generally linear relationship between OG determined by osmolality and the OG estimated using measured concentrations of acetone and toxic alcohols.