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] 4.0 mEq/L or greater. AG K and cAG K were evaluated against 12,341 data sets for their ability to detect [Lactate] > 4.0 mEq/L. Results Analysis of Eq. (1) revealed r 2  = 0.5950, p k  > 15 mEq/L exhibited a sensitivity of 93.0% [95% CI: 91.3–94.5] in detecting [Lactate] > 4.0 mEq/L, whereas AG K  > 15 mEq/L exhibited a sensitivity of only 70.4% [67.5–73.2]. Additionally, [Lactate] > 4.0 mEq/L and cAG K  > 20 mEq/L were each strongly associated with intensive care unit mortality (χ 2  > 200, p Conclusions In LA, cAG K is more sensitive than AG K in predicting [Lactate] > 4.0 mEq/L.