Quantitative relationships among plasma lactate, inorganic phosphorus, albumin, unmeasured anions and the anion gap in lactic acidosis

Abstract

Background: Quantitative relationships among plasma [Lactate], [Pi], [Albumin], unmeasured anions ([UA]) and the anion gap (AG_K) 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_K=[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_K: (2) cAG_K=[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_K and cAG_K were evaluated against 12,341 data sets for their ability to detect [Lactate]>4.0mEq/L.

Results: Analysis of Eq. (1) revealed r²=0.5950, p<0.001. cAG_k>15mEq/L exhibited a sensitivity of 93.0% [95% CI: 91.3-94.5] in detecting [Lactate]>4.0mEq/L, whereas AG_K>15mEq/L exhibited a sensitivity of only 70.4% [67.5-73.2]. Additionally, [Lactate]>4.0mEq/L and cAG_K>20mEq/L were each strongly associated with intensive care unit mortality (χ²>200, p<0.0001 for each).

Conclusions: In LA, cAG_K is more sensitive than AG_K in predicting [Lactate]>4.0mEq/L.