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      Reply by Cove and Kellum to Swenson

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          From the Editorialists: We thank Prof. Swenson for his well-articulated letter. We conceded in our editorial that the Stewart approach doesn’t provide a strong mechanistic explanation (1), and therefore we also agree it doesn’t eliminate a mechanistic role of bicarbonate. Rather, the Stewart approach provides a unifying explanation of the factors determining plasma pH by incorporating the role of electrolytes, plasma proteins, and carbon dioxide in all forms, including bicarbonate. Whether one considers bicarbonate to be dependent and Pco 2 independent, or vice versa, depends on the system under examination. Thus, we do not think this a useful classification and avoided the terms in our editorial because we’ve shown Pco 2 behaves like a dependent molecule under some circumstances (2). However, the classification does serve the purpose of drawing attention to the fact that Pco 2 and HCO3 are not independent of each other. Furthermore, the Stewart approach is not at odds with our understanding of membrane ion transporters; instead, it provides a more complete understanding of their function (3). In the paper by Zanella and colleagues, normal pH was restored after induction of acidosis by removing chloride to increase the strong ion difference; this also led to an increased bicarbonate level (4). Both of these changes can be easily understood with the Stewart approach, whereas a bicarbonate-centric approach focuses only on the bicarbonate change that occurred. Therefore, if we simply considered the information on the blood gas, we could only classify the acid–base changes in the Zanella experiments as metabolic, respiratory, or mixed, but we would be unable to describe what had caused the observed changes. Similarly, in clinical practice, a bicarbonate-centered approach allows us to identify the presence of an acid–base derangement as effectively as the Stewart approach. However, the Stewart approach provides a more precise classification of the acid–base changes, even in the studies referenced by Prof. Swenson (5). Such precision is important in clinical practice where, for example, the impact of choice of resuscitation fluids on acid–base status needs to be considered. We flatly reject the assertion that teaching the Stewart approach is difficult or that it leads to increased costs and blood loss. In fact, the variables needed to apply the approach are routinely measured already (6). The value of the approach comes from the ability to understand the relative contributing effects of simultaneous abnormalities on the final observed pH, such as elevated lactate, hypoalbuminemia, and electrolyte abnormalities, in a way that bicarbonate-centric understanding cannot (7).

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          Most cited references 7

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          Comparison of three different methods of evaluation of metabolic acid-base disorders.

          The Stewart approach states that pH is primarily determined by Pco2, strong ion difference (SID), and nonvolatile weak acids. This method might identify severe metabolic disturbances that go undetected by traditional analysis. Our goal was to compare diagnostic and prognostic performances of the Stewart approach with a) the traditional analysis based on bicarbonate (HCO3) and base excess (BE); and b) an approach relying on HCO3, BE, and albumin-corrected anion gap (AGcorrected). Prospective observational study. A university-affiliated hospital intensive care unit (ICU). Nine hundred thirty-five patients admitted to the ICU. None. The Stewart approach detected an arterial metabolic alteration in 131 (14%) of patients with normal HCO3- and BE, including 120 (92%) patients with metabolic acidosis. However, 108 (90%) of these patients had an increased AGcorrected. The Stewart approach permitted the additional diagnosis of metabolic acidosis in only 12 (1%) patients with normal HCO3, BE, and AGcorrected. On the other hand, the Stewart approach failed to identify 27 (3%) patients with alterations otherwise observed with the use of HCO3-, BE, and AGcorrected (16 cases of acidosis and 11 of alkalosis). SID and BE, and strong ion gap (SIG) and AGcorrected, were tightly correlated (R2 = .86 and .97, p < .0001 for both) with narrow 95% limits of agreement (8 and 3 mmol/L, respectively). Areas under receiver operating characteristic curves to predict 30-day mortality were 0.83, 0.62, 0.61, 0.60, 0.57, 0.56, and 0.67 for Sepsis-related Organ Failure Assessment (SOFA) score, SIG, AGcorrected, SID, BE, HCO3-, and lactates, respectively (SOFA vs. the rest, p < .0001). In this large group of critically ill patients, diagnostic performance of the Stewart approach exceeded that of HCO3- and BE. However, when AGcorrected was included in the analysis, the Stewart approach did not offer any diagnostic or prognostic advantages.
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            Stewart's quantitative acid-base chemistry: applications in biology and medicine.

             V FENCL,  I. D. Leith (1992)
            We review P.A. Stewart's quantitative approach to acid-base chemistry, starting with its historical context. We outline its implications for cellular and membrane processes in acid-base physiology; discuss its contributions to the understanding and analysis of acid-base phenomena; show how it can be applied in clinical problems; and propose a classification of clinical acid-base disturbances based on this general approach.
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              Stewart Acid-Base: A Simplified Bedside Approach.

               David Story (2016)

                Author and article information

                Am J Respir Crit Care Med
                Am. J. Respir. Crit. Care Med
                American Journal of Respiratory and Critical Care Medicine
                American Thoracic Society
                15 September 2020
                15 September 2020
                15 September 2020
                15 September 2020
                : 202
                : 6
                : 907-908
                [ 1 ]National University of Singapore

                Singapore, Singapore

                [ 2 ]University of Pittsburgh

                Pittsburgh, Pennsylvania
                Author notes
                [* ]Corresponding author (e-mail: mdcmec@ ).
                Copyright © 2020 by the American Thoracic Society

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 ( For commercial usage and reprints, please contact Diane Gern ( dgern@ ).

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