The Δ Anion Gap/Δ Bicarbonate Ratio in Early Lactic Acidosis: Time for Another Delta?

The ratio of Δ anion gap and Δ bicarbonate (ΔAG/ΔHCO₃) is used to detect coexisting acid-base disorders in patients with high anion gap metabolic acidosis. Classic teaching holds that, in lactic acidosis, the ΔAG/ΔHCO₃ is 1:1 within the first few hours of onset and subsequently rises to 1.8:1. However, this classic 1:1 stoichiometry in early lactic acidosis was derived primarily from animal models and only limited human data. The objective of this study was to examine the ΔAG/ΔHCO₃ within the first hours of the development of lactic acidosis.

Data were obtained prospectively from a convenience sample of adult (age >18 years) trauma-designated patients at a single level-1 trauma center. Venous samples, including a chemistry panel and serum lactate, were drawn before initiation of intravenous fluid resuscitation.

A total of 108 patients were included. Of these, 63 patients had normal serum lactate levels (≤2.1 mmol/L) with a mean AG of 7.1 mEq/L, the value used to calculate subsequent ΔAG values. ΔAG/ΔHCO₃ was calculated for 45 patients who had elevated serum lactate levels (>2.1 mmol/L). The mean ΔAG/ΔHCO₃ for all patients with elevated serum lactate levels was 1.86 (SD, 1.40).

The mean ΔAG/ΔHCO₃ was 1.86 within the first hours of the development of lactic acidosis due to hypovolemic shock, confirming a small prior human study. This contradicts the traditional belief that, in lactic acidosis, the ΔAG/ΔHCO₃ is 1:1 within the first several hours. The classic 1:1 stoichiometry was determined on the basis of animal models in which lactic acid is infused into the extracellular space, facilitating extracellular buffering of protons by bicarbonate. In contrast, our results demonstrate a higher initial ΔAG/ΔHCO₃ ratio in early endogenous lactic acidosis in humans. Our analysis indicates this is likely due to unmeasured anions contributing to an elevation in AG.