Serum Sodium Concentration and Tonicity in Hyperglycemic Crises: Major Influences and Treatment Implications.

Abstract

Maintenance of the volume of all cells, particularly those of the central nervous system, is critical for their function and survival.1, 2, 3, 4, 5, 6 Tonicity (ie, effective osmolarity) of a solution refers to its property to cause osmotic fluid shifts into or out of cells suspended in it. Direct determination of serum tonicity is not readily available for clinical applications.6 Serum sodium concentration ([Na]S) is the main parameter used as a surrogate value for serum tonicity.5, 6, 7 The only direct information provided by [Na]S is whether serum tonicity is normal (the volume of cells exposed to a serum with normal [Na]S is not affected), low (the volume of cells exposed to a serum with low [Na]S increases by osmotic intracellular transfer of water), or high (the volume of cells exposed to a serum with high [Na]S decreases by osmotic transfer of water out of the cells).6, 7 In a pivotal study, Edelman and coinvestigators identified total body sodium, total body potassium, and total body water as the universal determinants of [Na]S in patients with various states potentially associated with extracellular volume disturbances.8 Abnormalities in [Na]S usually result from changes in the external balance of one of its 3 determinants or a combination thereof. The relations between [Na]S and total body sodium, total body potassium, and total body water have been expressed by various formulas. The original Edelman formula expresses sodium concentration in plasma water.8 The Nguyen and Kurtz formula expresses sodium concentration in plasma, which is essentially equal to [Na]S.9 Nguyen and Kurtz developed their formula by multiplying the components of the Edelman formula by a correction coefficient equal to 0.93, which represents the normal plasma water fraction. The Rose formula, which represents a simplified version of the Edelman formula, expresses [Na]S as the fraction (total body sodium plus total body potassium) over total body water.10 Formulas calculating the tonicity of replacement solutions for correction of dysnatremias applied in clinical practice11, 12, 13, 14 are based on the Rose formula, which will also be the basis of the calculations in this review. The principle that underlies the distribution of body water in the 2 major body‐fluid compartments states that the intracellular/extracellular volume ratio is equal to the intracellular/extracellular solute ratio.15 This relationship is a direct consequence of Peter's osmotic principle, which states that in the steady state, solute concentration (osmolality) is equal in the intracellular and extracellular fluids.16 Total body sodium and potassium represent the major solutes in body fluids: sodium is essentially restricted in the extracellular compartment and potassium in the intracellular compartment. Consequently, total body sodium is a measure of effective extracellular solutes, whereas total body potassium represents the effective intracellular solutes. Hyperglycemic crises create complex disturbances in body water and its distribution between the intracellular and extracellular compartments, in addition to tonicity problems not reflected directly in [Na]S. This review analyzes the pathogenesis and treatment of hyperglycemic hypertonicity.