Buffers in intravenous solutions: is the source of bicarbonate a source of confusion?

There is a widespread belief that organic sodium salts included in intravenous solutions serve as bicarbonate precursors, and that this mechanism explains their effects on plasma pH. We aimed to explain why the effect of organic anions, such as citrate, acetate, gluconate, and lactate on the acid-base balance is independent of bicarbonate generation. For this purpose, we mainly focused on regional citrate anticoagulation (RCA). The sodium load provided with these buffers and its contribution to the plasma strong ion difference is a more suitable model for explaining and predicting their alkalinizing effect. Moreover, the bicarbonate generated from the metabolization of these buffers via the Krebs cycle results from CO₂ dissolution in water, and thus yields bicarbonate together with a proton (H⁺). As such, metabolization of these buffers does not cause alkalosis per se.