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Clin Chem. 2006 Apr;52(4):737-9. Epub 2006 Feb 2.

Osmolality gaps: diagnostic accuracy and long-term variability.

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(Department of Clinical Biochemistry, St. Boniface General Hospital, and University of Manitoba Medical School, Winnipeg, Manitoba, Canada.



The osmolal gap (OG) is a screening test for the detection of toxic volatiles such as methanol and ethylene glycol. We used mean values of patient data to assess the diagnostic accuracy and long-term stability of OG measurements.


In a prospective study period in 2003, all requests for volatiles had OGs calculated and quality-control samples were analyzed for OG. ROC curves were constructed to determine whether OG could predict the presence of toxic volatiles in serum. This was also done in a retrospective study for data from 1996 to 2004. Our laboratory database was searched for all emergency room patients for the period of 1996 to 2004 who had tests ordered that allowed us to calculate OGs.


For the prospective study period in 2003, the ROC areas indicated that we could accurately predict the presence of toxic volatiles but at markedly different decision cutpoints depending on the formula used. These cutpoints ranged from +10 to +33 mosmol/kg. In the retrospective study, the mean OGs in the patient population for each of the 3 formulas increased by 12 mosmol/kg from 1996 to 2004. For this reason, the diagnostic accuracy was poor when all data were analyzed together.


Under properly controlled conditions, the OG has high sensitivity and specificity for detection of poisoning with some volatiles. Over the long term, however, use of the reference interval of -10 to +10 mosmol/kg yields poor diagnostic accuracy because mean OGs are not constant over time. Bedside calculation is not advisable.

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