To the Editor:—

I read with great interest the editorial of Dr. Prough 1about articles by Liskaser et al. , 2Rehm et al. , 3and Waters and Bernstein. 4What I found most interesting was that these different authors did not agree on the etiology of fluid-induced metabolic acidosis. I agree with Dr. Prough’s summary that dilution of bicarbonate from extracellular volume expansion has at least a partial role in fluid-administered metabolic acidosis.

The study of Waters and Bernstein 4seems to refute the editorial of Dr. Prough 1by concluding that chloride and not volume expansion causes metabolic acidosis. They based their conclusion on their findings that hetastarch (containing 154 mEq/l chloride) caused metabolic acidosis and that equivalent amounts of albumin (containing 93 mEq/l) did not cause metabolic acidosis. However, albumin contains pH buffers, including sodium bicarbonate, which increase bicarbonate concentrations and thus may limit metabolic acidosis from volume expansion.

The study of Liskaser et al.  2about cardiopulmonary pump prime found that plasmalyte (98 mEq/l chloride) and polygeline–Ringer’s solution (151 mEq/l chloride) both caused the equivalent extent of metabolic acidosis when measured immediately after the start of cardiopulmonary bypass. 2The most likely reason for the plasmalyte prime’s causing a metabolic acidosis is simply a dilution of bicarbonate from a sudden extracellular volume expansion combined with the acetate and gluconate in plasmalyte not having time to be metabolized by the liver to form bicarbonate. The study of Liskaser et al.  2shows how such solutions as lactated Ringer’s or plasmalyte limit metabolic acidosis primarily from lactate, gluconate, and acetate contained in these solutions being metabolized to form additional bicarbonate and not from these solutions containing lower chloride concentrations.

This controversy about the etiology of metabolic acidosis from fluid administration also occurred approximately 3 yr ago in Anesthesiology with four letters to the editor based on a case report we wrote describing “dilutional acidosis.”5In our response to these letters, we mentioned a study performed over 30 yr ago, which was not mentioned in any of these articles. 6,7Asano et al.  7found that marked metabolic acidosis occurred when 5% dextrose and water (D5W) were administered to dogs. No cations or anions were administered, but metabolic acidosis occurred. Furthermore, dogs to which equivalent amounts of normal saline were administered had the same extent of metabolic acidosis as those dogs that received D5W. From that study, we concluded in our reply letter that simple volume expansion with dilution of bicarbonate was the most likely cause of metabolic acidosis.

I would appreciate any of the authors’ comments about the study of Asano et al.  7and about whether Stewart’s analysis of strong ions or actual simple dilution of bicarbonate explains the findings of this study.

Prough DS: Acidosis associated with saline administration: Dilution or delusion? A nesthesiology 2000; 93: 1167–9
Liskaser FJ, Bellomo R, Hayhoe M, Story D, Poustie S, Smith B, Letis A, Bennett M: Role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass–associated acidosis. A nesthesiology 2000; 93: 1170–3
Rehm M, Orth V, Scheingraber S, Kreimeier U, Brechtelsbauer H, Udilo F: Acid–base changes caused by 5% albumin versus  6% hydroxyethyl starch solution in patients undergoing acute normovolemic hemodilution. A nesthesiology 2000; 93: 1174–83
Waters JH, Bernstein CA: Dilutional acidosis following hetastarch or albumin in healthy volunteers. A nesthesiology 2000; 93: 1184–7
Mathes DD, Morell RC, Rohr MS: Dilutional acidosis: Is it a real clinical entity? (letter). A nesthesiology 1997; 86: 501–3
Mathes DD, Morell RC: Dilutional acidosis: Is it a real clinical entity? (reply). A nesthesiology 1997; 87: 1013–4
Asano S, Kato E, Yamauchi M, Ozawa Y, Iwasa M, Wada T, Hasegawa H: The mechanism of acidosis caused by infusion of saline solution. Lancet 1966; 1: 1245–6