A Comparison of Whole Blood and Plasma Osmolality and Osmolarity

Background Substituting whole blood osmolality for plasma osmolality could expedite treatments otherwise delayed by the time required to separate erythrocytes from plasma. The purpose of this study was to compare the measured osmolality (mmol/kg) and calculated osmolarity (mmol/l) of whole blood and plasma. Methods The osmolality of whole blood and plasma was measured using freezing point depression by micro‐osmometer and osmolarity calculated from biosensor measures of sodium, glucose, and blood urea nitrogen. The influence of sample volume was also investigated post hoc by comparing measured osmolality at 20 and 250 μl. Results Sixty‐two volunteers provided 168 paired whole blood and plasma samples for analysis. The mean difference (whole blood − plasma; ±standard deviation) in osmolality was 10 ± 3 mmol/kg. Whole blood was greater than plasma in 168 of 168 cases (100%) and data distributions overlapped by 27%. The mean difference in osmolarity was 0 ± 2 mmol/l. Whole blood was greater than plasma in 90 of 168 cases (56%) and data distributions overlapped by 90%. The osmol gap (osmolality − osmolarity) was 16 ± 6 mmol for whole blood and 7 ± 5 mmol for plasma. Ten volunteers were tested on one occasion post hoc to investigate the potential effects of sample volume. The difference between whole blood and plasma was reduced to 3 ± 2 mmol/kg with a larger (250 μl vs. 20 μl) sample volume. Conclusions This investigation provides strong evidence that whole blood and plasma osmolality are not interchangeable measurements when a 20 μl sample is used.