Fate of Sodium in Sodium Bicarbonate Infusions in Acid-Base Disorders – A New Analysis of Old Data

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Adrogué HJ, Awan AA, Madias NE: Sodium Fate after Sodium Bicarbonate Infusion: Influence of Altered Acid-Base Status. American Journal of Nephrology DOI 10.1159/000506274


It is well known that the space of distribution of bicarbonate anion (HCO3) following intravenous infusion of hypertonic sodium bicarbonate is independent of blood pH but is highly correlated with the pre-infusion extracellular HCO3 concentration. In hypobicarbonatemic states (metabolic acidosis and respiratory acidosis) the apparent HCO3 space exceeds that of total body water. The fate of the co-administered sodium cation (Na+) has not been investigated.

Adrogué et al. [1] addressed this missing information by re-analyzing the data from prior experiments in dogs with a variety of acid-base disorders. The Na+ space of distribution differed among the four acid-base disorders examined (metabolic acidosis and alkalosis, and respiratory alkalosis and acidosis). It increased above total body water in the hypobicarbonatemic groups, independent of blood pH, similar to that previously found for the HCO3 space of distribution. This points in the direction of an osmotic inactivation of the infused Na+ in hypobicarbonatemic, but not hyperbicarbonatemic or normobicarbonatemic states. This buffering is an initial but not a progressive phenomenon, as displayed by serial observations. Because of the similarity of the fate of administered Na+ and HCO3, the authors propose that they may be linked phenomena involving non-bicarbonate buffers in the extracellular fluids/matrix, also involving Na+/H+ exchange via the NHE1 exchanger. The fate of administered Na+ seems to be driven by the fate of HCO3, not vice versa. These findings also help to explain the differences of urinary Na+ excretion when hypertonic sodium bicarbonate is administered in hypobicarbonatemic as compared to hyperbicarbonatemic states.

This is a very stimulating and rewarding paper to read. It also recalls a version of a common adage: “Old and good data never dies” (in this case almost 40-year-old data) – it just awaits a re-analysis by curious and careful investigators. Kudos to Dr. Adrogué and his coworkers for their efforts.


Richard Glassock



[1] Adrogué HJ, Brensilver J, Cohen JJ, Madias NE: Influence of steady-state alterations in acid-base equilibrium on the fate of administered bicarbonate in the dog. J Clin Invest. 1983;71:867–83.

Quoted Karger Article

Sodium Fate after Sodium Bicarbonate Infusion: Influence of Altered Acid-Base Status