Unmeasured Organic Anions as Predictors of Clinical Outcomes in Lactic Acidosis due to Sepsis

Background and Objectives: In lactic acidosis, lactate can only explain 30% of the variance in the anion gap (AG), and the elevated AG not explained by lactate is due to unmeasured organic anions (UOAs). Some studies using less precise surrogates for UOA have suggested that UOA may predict clinical outcomes better than lactate. The aim of this study was to determine whether UOA predicts clinical outcomes better than lactate levels. Design, Setting, Participants, & Measurements: This was a retrospective cohort study of adult ICU patients with sepsis. Baseline AG and albumin measurements were obtained. An albumin-corrected delta AG was calculated. UOAs were estimated using the formula: Delta AG – serum lactate. A multivariate logistic regression model with its respective ROC curve was constructed to explore the relationship between in-hospital mortality, UOA, and lactate. Results: 526 patients were included. In the combined model examining both lactate and UOA, the odds ratio (OR) [95% CI] for predicting ICU length of stay (LOS) was 1.050 [1.029-1.072] and 1.022 [1.009-1.035], respectively; the OR [95% CI] for predicting in-hospital mortality was 1.224 [1.104-1.358] and 0.997 [0.943-1.054], respectively. The ROC curve for in-hospital mortality demonstrated that the Area Under the Curve (AUC) for lactate, UOA, and combined lactate and UOA was 0.7726, 0.7486, and 0.7732, respectively. The AUC for combined lactate and UOA were not statistically significantly higher than the AUC for lactate alone (P .9193). Conclusions: As expected, serum lactate predicted both ICU LOS and in-hospital mortality. UOA did predict ICU LOS, although the reason for this association is not known. UOA did not predict in-hospital mortality based on the OR and the ROC curve's AUC, contrary to some previous studies. However, our study used a more precise quantitative estimate of UOA, including the use of baseline albumin-corrected AG. Prior studies attempting to identify UOA have identified Krebs cycle intermediates including citrate and isocitrate, suggesting that in our study these anions associated with the Krebs cycle contributed to the UOA.