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.

Relationship Between the Anion Gap and Serum Lactate in Hypovolemic Shock.

Background and objectives: Previous studies evaluating patients in the Intensive Care Unit with established lactic acidosis determined that the anion gap is an insensitive screening tool for elevated blood lactate. No prior study has examined the relationship between anion gap and serum lactate within the first hours of the development of lactic acidosis. Design, setting, participants, & measurements: Data were obtained prospectively from a convenience sample of adult trauma patients at a single level 1 trauma center. Venous samples were drawn prior to initiation of intravenous fluid resuscitation. A linear regression model was constructed to assess the relationship between serum lactate and anion gap, and 95% prediction intervals were computed. Logistic regression models were constructed to determine the sensitivity and specificity for several different anion gap and lactate cutpoints. Results: 128 patients with elevated serum lactate levels (>2.1 mmol/L) and 63 patients with normal serum lactate levels (< 2.1 mmol/L) were included. The sensitivity of an elevated anion gap (> 10) to reveal hyperlactatemia was only 43% whereas specificity was 84%. Sensitivity improved if the upper limit of normal anion gap was lowered and with increasing levels of serum lactate. The coefficient of determination between serum lactate level and AG yielded an R2 of 0.30 (p < 0.001) and the slope of this relationship was 2.185 with a 95% confidence interval of 2.011-2.359. The mean 95% prediction interval was + 8.9. Conclusions: Within the first hour of the development of lactic acidosis due to hypovolemic shock, the anion gap was not a sensitive indicator of an elevated serum lactate level, but it was fairly specific. The anion gap increased to a greater extent than the serum lactate, the 95% mean prediction interval was wide and approximately 70% of the change in anion gap could not be explained by increases in serum lactate, suggesting that other anions contribute to the anion gap in lactic acidosis.

Assessing Acid-Base Status in Circulatory Failure: Relationship Between Arterial and Peripheral Venous Blood Gas Measurements in Hypovolemic Shock.

BACKGROUND AND OBJECTIVES: In severe circulatory failure agreement between arterial and mixed venous or central venous values is poor; venous values are more reflective of tissue acid-base imbalance. No prior study has examined the relationship between peripheral venous blood gas (VBG) values and arterial blood gas (ABG) values in hemodynamic compromise. The objective of this study was to examine the correlation between hemodynamic parameters, specifically systolic blood pressure (SBP) and the arterial-peripheral venous (A-PV) difference for all commonly used acid-base parameters (pH, Pco 2, and bicarbonate). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Data were obtained prospectively from adult patients with trauma. When an ABG was obtained for clinical purposes, a VBG was drawn as soon as possible. Patients were excluded if the ABG and VBG were drawn >10 minutes apart. RESULTS: The correlations between A-PV pH, A-PV Pco 2, and A-PV bicarbonate and SBP were not statistically significant (P = .55, .17, and .09, respectively). Although patients with hypotension had a lower mean arterial and peripheral venous pH and bicarbonate compared to hemodynamically stable patients, mean A-PV differences for pH and Pco 2 were not statistically different (P = .24 and .16, respectively) between hypotensive and normotensive groups. CONCLUSIONS: In hypovolemic shock, the peripheral VBG does not demonstrate a higher CO2 concentration and lower pH compared to arterial blood. Therefore, the peripheral VBG is not a surrogate for the tissue acid-base status in hypovolemic shock, likely due to peripheral vasoconstriction and central shunting of blood to essential organs. This contrasts with the selective venous respiratory acidosis previously demonstrated in central venous and mixed venous measurements in circulatory failure, which is more reflective of acid-base imbalance at the tissue level than arterial blood. Further work needs to be done to better define the relationship between ABG and both central and peripheral VBG values in various types of shock.

The Δ Anion Gap/Δ Bicarbonate Ratio in Lactic Acidosis: Time for a New Baseline?

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. The ΔAG/ΔHCO3 ratio of 1.6-1.8:1 in lactic acidosis is derived from limited data using mean normal values for AG and serum HCO3. The objective of this study was to be the first to examine the ΔAG/ΔHCO3 using each patient's individual baseline AG and serum HCO3. METHODS: This was a retrospective cohort study of adult ICU patients with sepsis. Lab data from simultaneously drawn chemistry panel, including anion gap and serum lactate on admission to the ICU was obtained. Baseline AG, HCO3 and albumin measurements were obtained 1-24 months prior to ICU admission. The ΔAG/ΔHCO3 was calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3. RESULTS: 344 patients were included. 128 patients had normal serum lactate levels (≤1.9 mmol/L) and 216 patients had elevated serum lactate levels (>1.9 mmol/L). ΔAG/ΔHCO3 was calculated for the 216 patients who had elevated serum lactate levels (>1.9 mmol/L). The mean ΔAG/ΔHCO3 for all patients with elevated serum lactate levels was 1.20 (SD 1.50). CONCLUSIONS: The mean ΔAG/ΔHCO3 calculated using an albumin-corrected anion gap and each patient's individual baseline AG and serum HCO3 was 1.20. The ΔAG/ΔHCO3 reported in prior literature which used mean normal AG and serum HCO3 was 1.6-1.8, highlighting that use of mean normal values affects the calculation of the ΔAG/ΔHCO3 and subsequent conclusions about underlying pathophysiology. The use of these mean normal values can result in misdiagnosis of complex acid-base disorders and inappropriate treatment. Our analysis indicates that the elevated ΔAG/ΔHCO3 is likely due to unmeasured anions contributing to an elevation in AG.

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

Background: 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. Methods: 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. Results: 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). 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 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.