The Cleveland Clinic Foundation, Cleveland, Ohio. watersj@cff.orgIn Reply:I would like to thank Drs. Roth and Mathes for their interest in my recent article. 1First, I would like to address the comments of Dr. Roth. He correctly points out the importance of differentiating between intracellular and extracellular mechanisms for the creation of an acidosis, concluding that an extracellular mechanism probably has minimal impact on outcome. Like Dr. Roth, I believe that it is critical to make this distinction. The importance of this differentiation is best shown by the many publications that have evaluated the intracellular-to-extracellular potassium flux after an acid–base change. These articles describe a wide spectrum of mechanisms for creating an acid–base change. As a result, each article reaches a different conclusion regarding the effect of acid–base change on intracellular or extracellular potassium movement. 2I agree with Dr. Roth in his speculation that the impact on outcome of a dilutional acidosis created through the administration of 0.9% saline solution is probably limited; however, there is some evidence that 0.9% saline solution may have some effect on perioperative blood loss. In a study of patients undergoing major blood loss surgery, Martin et al. 3found greater blood loss in patients to whom hetastarch in a normal saline solution was administered when compared with patients to whom hetastarch in a buffered electrolyte solution was administered. They suggested that the hyperchloremic acidosis after the normal saline–containing solution was responsible. Gan et al. 4reported a difference in blood loss between two similar study groups. Like Dr. Roth, I believe that there are more questions to be answered about the effect of 0.9% saline solution administration.The question raised by Dr. Mathes relating to a study by Asano et al. 5is more difficult to address. In this study, a metabolic acidosis was found in dogs to which 5% dextrose in water was administered. An explanation for this acidosis using Stewart’s analysis requires some understanding of Stewart’s acid–base theory. According to Stewart, 6,7the acid–base status is determined by the strong ion difference (SID), the albumin concentration, and the partial pressure of carbon dioxide (Pco2). Respiratory acid–base change results from changes in Pco2, whereas metabolic problems relate to changes in albumin concentration and the SID. The weak electrolyte, albumin, needs to be changed significantly before it has significant impact on acid–base status. For this reason, in the operating room, most metabolic derangement can be explained by changes in the SID. The SID is the difference in concentrations of Na+, K+, CI−, and lactic acid. The difference between the cation and anion concentrations can be affected by the amount of free water in which the electrolytes are dissolved. This relation between the SID and water is the explanation for the findings of Asano et al. 5Understanding of this concept is best aided by an example. If one were to take a liter of water containing only sodium and chloride, the law of electroneutrality (∑cations =∑anions) must be maintained by dissociation of water. For example, if a liter of water contains 140 mEq/l sodium and 110 mEq/l chloride, the SID of that solution is 30 mEq. This positive charge difference would need to be balanced by water dissociation. If we were to add another liter of water without adding any more electrolytes, the solution would contain 70 mEq/l sodium and 55 mEq/l chloride, and the SID would be 15 mEq. Because we have decreased the positive charge contribution of the SID from 30 mEq to 15 mEq, a decrease in [OH−] would occur with an increase in [H+], and a true dilutional acidosis would be seen. This phenomena is of importance during transurethral resection of the prostate where large volumes of free water can be absorbed. 8This is how I would explain the findings of Asano et al. 5using Stewart’s analysis.