2). Throughout the range of serum lactate and pH, the Sunitinib Sigma quantity of unmeasured anions is Nilotinib considerable. The mean ALCAG for the entire cohort was 12.6 ± 3.61. Given that patients with toxic, ingestions, uremia, and those with ketoacidosis were excluded and that lactate and serum albumin are accounted for in the ALCAG

equation, the amount of unmeasured anions in this cohort of critically ill patients is elevated. In order to better quantify these anions, the Fencl-Stewart methodology Inhibitors,research,lifescience,medical for acid-base assessment would be preferable.[20] In this approach, the unmeasured anions can be assessed because the strong ion difference (apparent and effective) is directly measured. This methodology involves the cotemporaneous measurement of the serum sodium, potassium, magnesium, chloride, lactate, pH, phosphorus, pCO2, and serum albumin.[21] In this cohort, the magnesium, phosphorus,

and calcium were not consistently available in order to measure the true quantity of the unmeasured anions (strong ion gap). Because we do not have all the requisite information to calculate the strong ion gap (SIG), Inhibitors,research,lifescience,medical we cannot be certain Inhibitors,research,lifescience,medical that the ALCAG is representative of the SIG. In one small study, the SIG and the ALCAG were highly correlated (r2 = 0.934, p < 0.0001).[18] We hypothesize that the ALCAG may be an easy bedside measurement that may approximate the SIG in patients who are critically ill. Further research of this relationship Inhibitors,research,lifescience,medical in large diverse populations is warranted. The etiology of the unmeasured anions commonly found in critically ill patients has been described. In patients with lactic acidosis and in patients with 'unexplained anion gap acidosis' and normal serum lactates, plasma concentrations of acids associated with the Krebs cycle are significantly elevated.[22] The unmeasured identified anions are: citrate, isocitrate, α-ketoglutarate, succinate, maleate, and d-lactate. Because these acids are often tri- and di- basic, smaller concentrations can have larger effects on the anion gap. Unmeasured anions as quantified

by the Fencl-Stewart Inhibitors,research,lifescience,medical methodology predict outcomes in critically ill patients better than serum lactate.[23] The etiology for why these anions are increased in critically ill patients is unknown, but mitochondrial dysfunction and cellular cytopathic AV-951 hypoxia as well as disordered glycolytic effects have been proposed.[22] We speculate that the quantity of these unmeasured anions in relationship to the serum lactate (unmeasured anions to lactate ratio) may provide a means for assessing the etiology of lactic acidosis and/or as a predictor of mortality. Further research is warranted. Figure 1 Albumin lactate corrected anion gap (ALCAG) v. serum lactate. Figure 2 Albumin lactate corrected anion gap (ALCAG) v. pH. Limitations Our study was conducted in 143 patients with over 497 cotemporaneous samples. Ideally we would have been able to perform this study in a larger population in order to maximize our power.