Edelman Revisited: Concepts, Achievements, and Challenges

Abstract

The key message from the 1958 Edelman study states that combinations of external gains or losses of sodium, potassium and water leading to an increase of the fraction (total body sodium plus total body potassium) over total body water will raise the serum sodium concentration ([Na]S), while external gains or losses leading to a decrease in this fraction will lower [Na]S. A variety of studies have supported this concept and current quantitative methods for correcting dysnatremias, including formulas calculating the volume of saline needed for a change in [Na]S are based on it. Not accounting for external losses of sodium, potassium and water during treatment and faulty values for body water inserted in the formulas predicting the change in [Na]S affect the accuracy of these formulas. Newly described factors potentially affecting the change in [Na]S during treatment of dysnatremias include the following: (a) exchanges during development or correction of dysnatremias between osmotically inactive sodium stored in tissues and osmotically active sodium in solution in body fluids; (b) chemical binding of part of body water to macromolecules which would decrease the amount of body water available for osmotic exchanges; and (c) genetic influences on the determination of sodium concentration in body fluids. The effects of these newer developments on the methods of treatment of dysnatremias are not well-established and will need extensive studying. Currently, monitoring of serum sodium concentration remains a critical step during treatment of dysnatremias.

Hypertonic Saline Infusion for Hyponatremia: Limitations of the Adrogué-Madias and Other Formulas

“…Table 2 presents the reported limitations of the original Adrogué-Madias formula. 5,23,27–49 The first four limitations in Table 2 have been examined in detail elsewhere. 5,7,8,23 In this report, they will be reviewed synoptically.…”

“…Genetic influences are major determinants of the range of [ Na ] and affect the development of dysnatremias. 5,35,46 A loss-of-function polymorphism of the osmoregulatory gene TRPV4 is a source of hyponatremia. 47 Hereditary polyanionic proteoglycan structure deviations alter the osmotically inactive compartment, for example, in subjects with hereditary multiple exostoses.…”

“…45 Neither the size of the part of body water in this exclusion zone nor whether rapid changes in [ Na ] affect the size of the exclusion zone are known. 5 Future studies should address these topics.…”

“…The Nguyen-Kurtz formulas were created to account for osmotic inactivation. 21 However, the accuracy of these formulas may be questioned because of the following two reasons: (1) the Edelman formula was developed without data from changes in [ Na ] 5 and (2) a repeated statistical analysis of the data used in the Edelman study by Oppelaaar and coinvestigators produced regression results substantially different from the Edelman formula. 49…”

“…A review of studies comparing the Adrogué-Madias and other formulas concluded that the accuracy of the formulas studied was reasonable on the average, although the ranges of the differences between predicted and actual [Na] 2 values were wide for all formulas; none showed clear superiority. 5 Limitations of the Adrogue ´-Madias Formula and Other Formulas Table 2 presents the reported limitations of the original Adrogué-Madias formula. 5,23, The first four limitations in Table 2 have been examined in detail elsewhere.…”