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      Use of Sodium-Chloride Difference and Corrected Anion Gap as Surrogates of Stewart Variables in Critically Ill Patients

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          Abstract

          Introduction

          To investigate whether the difference between sodium and chloride ([Na +] – [Cl ]) and anion gap corrected for albumin and lactate (AG corr) could be used as apparent strong ion difference (SID app) and strong ion gap (SIG) surrogates (respectively) in critically ill patients.

          Methods

          A total of 341 patients were prospectively observed; 161 were allocated to the modeling group, and 180 to the validation group. Simple regression analysis was used to construct a mathematical model between SID app and [Na +] – [Cl ] and between SIG and AG corr in the modeling group. Area under the receiver operating characteristic (ROC) curve was also measured. The mathematical models were tested in the validation group.

          Results

          in the modeling group, SID app and SIG were well predicted by [Na +] – [Cl ] and AG corr (R 2 = 0.973 and 0.96, respectively). Accuracy values of [Na +] – [Cl ] for the identification of SID app acidosis (<42.7 mEq/L) and alkalosis (>47.5 mEq/L) were 0.992 (95% confidence interval [CI], 0.963–1) and 0.998 (95%CI, 0.972–1), respectively. The accuracy of AG corr in revealing SIG acidosis (>8 mEq/L) was 0.974 (95%CI: 0.936–0.993). These results were validated by showing excellent correlations and good agreements between predicted and measured SID app and between predicted and measured SIG in the validation group (R 2 = 0.977; bias = 0±1.5 mEq/L and R 2 = 0.96; bias = −0.2±1.8 mEq/L, respectively).

          Conclusions

          SID app and SIG can be substituted by [Na +] – [Cl ] and by AG corr respectively in the diagnosis and management of acid-base disorders in critically ill patients.

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          Most cited references22

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          Statistical methods for assessing agreement between two methods of clinical measurement.

          In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old. Such investigations are often analysed inappropriately, notably by using correlation coefficients. The use of correlation is misleading. An alternative approach, based on graphical techniques and simple calculations, is described, together with the relation between this analysis and the assessment of repeatability.
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            Statistics review 13: Receiver operating characteristic curves

            This review introduces some commonly used methods for assessing the performance of a diagnostic test. The sensitivity, specificity and likelihood ratio of a test are discussed. The uses of the receiver operating characteristic curve and the area under the curve are explained.
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              The role of serum proteins in acid-base equilibria.

              Serum proteins act as weak acids and participate in acid-base balance. Their effects are imprecisely quantified; in particular, the roles of albumin and globulins need reevaluation. We approached the problem in three steps. First, in artificial solutions resembling serum but with human serum albumin as the only protein moiety, we varied the strong ion difference (SID), partial pressure of carbon dioxide (Pco2) and the concentration of albumin [( Alb]) and fixed the concentration of inorganic phosphate [( Pi]). We measured pH and derived the charges on albumin. Second, extending the work of Stewart (Stewart PA. How to understand acid-base. A quantitative acid-base primer for biology and medicine. New York: Elsevier, 1981:1-286), we developed a mathematical model that solves for pH and for the charges on albumin as functions of SID, Pco2, [Pi], and [Alb]. The calculated values fit the observed values well; that is, the model describes well the behavior of these solutions over a wide range of simulated complex acid-base disturbances. Finally, in human serum samples containing both albumin and globulins, we varied SID, Pco2, and total protein concentration [( TP]); we fixed [Pi] and then measured pH and derived the charges on proteins as above. When we applied to these data the computer model developed for albumin alone, the calculated pH and derived charges on albumin values agreed well with the observed pH and derived charges on proteins. We conclude first that human serum globulins play a negligible role in acid-base equilibria, and second, that in normal human serum at pH 7.40 with [TP] = 7 and [Alb] = 4.3 gm/dl, the charges attributed to proteins are approximately 12 mEq/L; this is substantially less than the value of approximately 17 mEq/L given by many contemporary texts, based on work of van Slyke et al. (van Slyke DD, Hastings AB, Hiller A, Sendroy J Jr. Studies of gas and electrolyte equilibria in blood. XIV. Amounts of alkali bound by serum albumin and globulin. J Biol Chem 1928;79:769-80). These findings should be considered when evaluating acid-base balance in patients with abnormal serum albumin concentration, for example, when interpreting values of the anion gap.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                13 February 2013
                : 8
                : 2
                : e56635
                Affiliations
                [1]Department of Intensive Care Unit, Centre Hospitalier du Dr. Schaffner, Lens, France
                University of Louisville, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JM SB. Performed the experiments: JM SB ML FP GG LT DT. Analyzed the data: JM. Contributed reagents/materials/analysis tools: JM SB. Wrote the paper: JM.

                Article
                PONE-D-12-32349
                10.1371/journal.pone.0056635
                3572048
                23418590
                6065a235-2cc9-4b50-8271-0a0c918b1e8a
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 October 2012
                : 11 January 2013
                Page count
                Pages: 8
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Renal System
                Renal Physiology
                Medicine
                Anatomy and Physiology
                Renal System
                Renal Physiology
                Critical Care and Emergency Medicine
                Acute Renal Failure
                Fluid Management
                Renal Critical Care
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Nephrology
                Acute Renal Failure
                Mineral Metabolism and the Kidney

                Uncategorized
                Uncategorized

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