Background: Quantitative relationships among plasma [Lactate], [Pi], [Albumin], unmeasured anions ([UA]) and the anion gap (AG) in lactic acidosis (LA) are not well defined.
Methods: A mathematical model featuring compensatory potassium and chloride shifts and respiratory changes in LA demonstrated: (1) AG=[Lactate]+Zp×[Pi]+2.4×[Albumin]+constant1+e, where Zp is a function of pH, and e reflects unmeasured anions and cations plus pH-related variations. Eq. (1) can be algebraically rearranged to incorporate the albumin-corrected anion gap, cAG: (2) cAG=[Lactate]+Zp×[Pi]+constant2+e. Eq. (1) was tested against 948 data sets from critically ill patients with [Lactate] 4.0mEq/L or greater. AG and cAG were evaluated against 12,341 data sets for their ability to detect [Lactate]>4.0mEq/L.
Results: Analysis of Eq. (1) revealed r=0.5950, p<0.001. cAG>15mEq/L exhibited a sensitivity of 93.0% [95% CI: 91.3-94.5] in detecting [Lactate]>4.0mEq/L, whereas AG>15mEq/L exhibited a sensitivity of only 70.4% [67.5-73.2]. Additionally, [Lactate]>4.0mEq/L and cAG>20mEq/L were each strongly associated with intensive care unit mortality (χ>200, p<0.0001 for each).
Conclusions: In LA, cAG is more sensitive than AG in predicting [Lactate]>4.0mEq/L.
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