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

Background: The ratio of delta anion gap and delta bicarbonate (ΔAG/ΔHCO3) is used to detect co-existing 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. Methods: Data were obtained prospectively from a convenience sample of adult trauma designated patients at a single level 1 trauma center. Venous samples, including a chemistry panel and serum lactate, were drawn prior to initiation of intravenous fluid resuscitation. Results: 108 patients were included. 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). Conclusions: 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 is based on 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 that this is likely due to unmeasured anions contributing to an elevation in AG.