To the Editor:—

Three recent articles and an editorial explain how an infusion of normal saline can cause a “dilutional acidosis.”1–4However, these studies do not address the difference between acidosis caused by iatrogenic infusion of normal saline and those caused by pathologic intracellular processes. These differences may have clinical relevance.

In caring for patients, we are often interested in gaining information about a patient’s metabolic status. Because most of the body’s metabolism is performed intracellularly and there is no practical method to obtain intracellular samples, we obtain a blood sample and presume it reflects what is occurring intracellularly. Typically, a metabolic acidosis reflects an intracellular metabolic derangement, which is eventually reflected in the acidification of the blood. The dilutional acidosis resulting from normal saline infusion does not reflect an intracellular metabolic derangement. Therefore, one would surmise the problems associated with dilutional acidosis are related only to the problems caused by the acidification of the blood per se , and perhaps intracellular acidification if there are pH shifts across cell membranes. Therefore, for the same degree of acidemia, a dilutional acidosis might be expected to be less worrisome than a metabolic acidosis caused by an intracellular metabolic derangement for at least two reasons. First, there is no other major primary metabolic derangement with a dilutional acidosis. Second, for the same degree of acidemia, one might expect a lesser intracellular pH decrease in the dilutional acidosis patient compared with a greater intracellular pH decrease in the metabolically deranged patient. In the dilutional acidosis patient, the initial pH change occurs extracellularly, and a lesser or delayed pH change would occur intracellularly. Conversely, in the metabolically deranged patient, the initial pH change occurs intracellularly, and a lesser or delayed change would occur extracellularly.

Situations can occur in which the metabolic acidosis can be caused both by an internal metabolic derangement and by fluid resuscitation with normal saline. Two examples are lactic acidosis from hypoperfusion and diabetic ketoacidosis; fluid resuscitation is required in both situations. If one is using the degree of acidemia to gauge the severity of illness, it may be difficult to determine how much of the acidosis is due to the probably more benign dilutional acidosis. A given degree of acidosis may imply a variable severity of illness, depending on how much of the acidosis is due to an internal metabolic derangement and how much is due to dilutional acidosis. Clinical criteria that consider blood pH may need to be reevaluated if normal saline infusion occurred.

Like most good studies, more questions are generated than answered. Although the determination of clinical relevance was not the intent of these studies, one of the articles commented, “The acidosis in both groups seems to be without major clinical relevance.”2From the perspective of a clinician, it would be helpful to have the following questions answered:

  • 1. What degree of dilutional acidosis, if any, is harmful?

  • 2. Is there a maximum degree of dilutional acidosis that can result just from normal saline administration?

  • 3. How long should it take for a dilutional acidosis to correct after normal saline infusion is discontinued?

  • 4. When should dilutional acidosis be treated?

  • 5. If treatment is indicated, would sodium bicarbonate, THAM, or both be appropriate for treating dilutional acidosis?

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
Prough DS: Acidosis associated with saline administration: Dilution or delusion? A nesthesiology 2000; 93: 1167–9