Mind the gap: shortcomings of the osmotic gap and a possible solution.

Background Measured (MO) and calculated osmotic concentrations (CO) and the osmotic gap (OG) are commonly used in the investigation of electrolyte and volume disturbances as well as in cases of suspected volatile ingestion. Methods We compared 38 published formulae for CO with MO on a large data-set ( n = 9466) and adjusted the CO with the result of a Passing-Bablok regression procedure. Validation of this adjustment was performed with a separate data-set ( n = 2082). Results All but one of the CO formulae underestimate MO due to a proportional bias (slope 0.67 to 0.95) and the OG limits were therefore not applicable throughout the observed range. Using Passing-Bablok regression to adjust the CO: CO#3  = (2 × Na+urea+glucose-14.54)/0.93. After adjustment, the mean OG was 0.3 mmol/L with a SD of 5.1 mmol/L across the measurement interval. The distribution of the OG could be fully explained by the analytical imprecision of the measured components. Conclusions Simple adjustment of the CO for the proportional underestimation of MO allows OG reference limits of approximately -10 to +10 mmol/L to be used, even in the upper ranges of CO in patients with suspected volatile ingestion.