Establishing Pragmatic Analytical Performance Specifications for Blood Beta-Hydroxybutyrate Testing

Background Currently, no authoritative guidelines exist recommending the analytical performance specification (APS) of blood beta-hydroxybutyrate (BOHB) testing in order to meet the clinical needs of patients. This study has applied existing diabetic ketoacidosis (DKA) BOHB diagnostic thresholds and the recommended rates of fall in BOHB concentrations during DKA treatment to establish pragmatic APSs for BOHB testing. Methods Required analytical performance was based on 2 clinical requirements: (a) to reliably distinguish between non-adjacent DKA BOHB diagnostic categories of <0.6, 0.6 to 1.5, 1.6 to 2.9, and >= 3 mmol/L, and (b) to be assured that a measured 0.5 mmol/L reduction in BOHB indicates the true concentration is at least falling (meaning >0 mmol/L decline). Results An analytical coefficient of variation (CV) of 99% certainty, assuming zero bias. In contrast, within-day CVs of 4.9%, 7.0%, and 9.1% at 3 mmol/L BOHB were required to assure truly falling ketone concentrations with 99% (optimal), 95% (desirable), and 90% (minimal) probability, respectively. These CVs are larger at lower BOHB concentrations and smaller at higher concentrations. Conclusions Reliable tracking of changes in BOHB during DKA treatment largely drives the requirement for analytical performance. These data can be used to guide minimal, desirable, and optimal performance targets for BOHB meters and laboratory assays.

Automated summary

Currently, there are no authoritative guidelines for the analytical performance specification (APS) of blood BOHB testing. This study establishes pragmatic APSs based on existing DKA BOHB diagnostic thresholds and recommended rates of fall in BOHB concentrations during DKA treatment. The reliable tracking of changes in BOHB during DKA treatment is the main driver for the requirement of analytical performance.