Acidosis associated with perioperative saline administration: dilution or delusion?

THE hypothesis that saline administration results in dilutional acidosis was advanced by Shires and Holman in 1948. The antithesis, that physiologic defense mechanisms prevent reduction of bicarbonate concentration ([HCO3 ]) to the extent predicted by simple dilution, followed approximately 20 yr later and generally was accepted by 1975. In the 1990s, a variety of case reports and clinical studies showed that perioperative administration of clinically relevant volumes of 0.9% saline was associated with substantial hypobicarbonatemia and hyperchloremia. However, if the concept of dilutional acidosis were valid, reductions of [HCO3 ] should be proportional to the extent of dilution. In the current issue of ANESTHESIOLOGY, three clinical studies suggest that actual [HCO3 ] is similar to changes in [HCO3 ] predicted on the basis of dilution. Together, they provide a sound basis for the synthesis that the term “dilutional acidosis” is not only an important clinical entity, but also an appropriate physiologic term. In the context of perioperative fluid administration, dilutional acidosis is metabolic acidosis that results from rapid administration of fluids that contain near-physiologic concentrations of sodium accompanied by anions (usually chloride) other than bicarbonate or bicarbonate precursors, such as lactate. The magnitude of acidosis is a consequence of several factors: the baseline volume and composition of plasma volume and extracellular volume (ECV); the volume, rate, and composition of administered fluid; the volume, rate, and composition of fluid losses; and physiologic modification of changes in extracellular composition (e.g., via transmembrane shifts, excretion, or metabolism). Although animal studies have involved volume expansion, hypervolemia is not necessary for the diagnosis of dilutional acidosis. Data previously reported in dogs undergoing rapid volume expansion with saline provide a useful background for clinical studies (table 1). In nephrectomized dogs, infusion of 50, 75, or 100 ml/kg saline decreased [HCO3 ] by less than half of that predicted based on dilution of ECV. Similarly, infusion of 105 ml/kg saline over 2 h decreased actual [HCO3 ] by only approximately one third of the predicted decrease. In contrast, each of the three studies in this issue of ANESTHESIOLOGY reports a reduction of [HCO3 ] by saline or other high-chloride solutions that approximates what would have been predicted based on simple dilution of extracellular [HCO3 ] (table 2). These reports build on previous perioperative studies in which the effects of saline infusion were potentially confounded by the effects of surgery and blood loss. Waters and Bernstein, Rehm et al., and Liskaser et al. chose experimental designs that more completely controlled important factors that could influence dilutional acidosis. Waters and Bernstein induced acute hypervolemia in volunteers with use of a 30-min colloid infusion (hetastarch in 0.9% saline or albumin in an unquantified diluent) and measured results immediately after infusion. Rehm et al. assessed acid–base changes 20 min after isovolemic hemodilution with colloid (hetastarch in 0.9% saline or albumin in a solution resembling 0.9% saline). This approach did not expand blood volume but expanded ECV and removed approximately 20 mEq bicarbonate. Liskaser et al. cleverly took advantage of the unique circumstances at the beginning of cardiopulmonary bypass, when priming volume is added short-term to the circulation. They evaluated acid–base status 2 min after initiation of cardiopulmonary bypass with a priming solution that contained either 151 mEq/l chloride or 98 mEq/l chloride plus acetate and gluconate. Measurements so soon after the onset of bypass permitted minimal time for equilibration throughout ECV, physiologic modification of acid–base status, or confounding fluid losses. In the three studies, the results that were interpreted most easily were those caused by infusion of hetastarch in 0.9% saline or initiation of bypass using the higher chloride priming solution. After rapid volume expansion This Editorial View accompanies the following three articles: Liskaser FJ, Bellomo R, Hayhoe M, Story D, Poustie S, Smith B, Letis A, Bennett M: The role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass–associated acidosis. ANESTHESIOLOGY 2000; 93:1170–3; Rehm M, Orth V, Scheingraber S, Kreimeier U, Brechtelsbauer H, Finsterer U: Acid–Base changes due to 5% albumin versus 6% hydroxyethylstarch solution in patients undergoing acute normovolemic hemodilution: A randomized prospective study. ANESTHESIOLOGY 2000; 93:1174–83; and Waters JH, Bernstein CA: Dilutional acidosis following hetastarch or albumin in healthy volunteers. ANESTHESIOLOGY 2000; 93:1184–7. r