In Reply:

We are grateful to have the opportunity to respond to the thoughtful comments by Drs. Mathes and Roth. Dr. Mathes asks for an interpretation of the results of the study of Asano et al.  1His main question is whether Stewart’s analysis 2of strong ions or simply the dilution of bicarbonate according to the classical approach by Sigaard-Andersen 3explains the findings of this study. Asano et al.  1infused very large amounts (3.5 ml · kg−1· min−1for 25 min) of 5% glucose or mannitol in dogs and observed an almost identical decrease in pH by infusing the same amount of 0.9% saline. The question whether volume changes of the extracellular space (and the dilution with bicarbonate-free solutions) or changes in the ionic composition of the extracellular space cause metabolic acid–base disturbances is interesting, but possibly more a philosophical than a physiologic one. Diluting the extracellular space (with probably any solution) should result in the combination of a change in the respective volume and  a change in the respective ionic composition. Recently, we demonstrated that during transurethral resection of the prostate and absorption of approximately 500 ml irrigation fluid, a moderate metabolic acidosis occurred. 4In this case, ion and bicarbonate-free irrigation fluid (consisting of 2% ethanol, 0.54% mannitol, and 2.7% sorbitol in water) was administered. In the study group (the group with a marked irrigant absorption), we observed not only volume changes (decrease in the hemoglobin concentration as an indication of an increase in the extracellular volume), but also changes in the strong ion difference (−3.9 mm) and in the amount of weak plasma acid (−1.5 mm). These changes sufficiently explained the observed acid–base changes by means of Stewart’s equations. However, to answer Dr. Mathes’ question, it would be necessary to investigate isolated changes in the strong ion difference, the amount of weak plasma acid, or both without changes in the volume of the extracellular space and to investigate changes in the volume without changes in the ionic composition of the extracellular space. However, we believe that such experiments are not possible in any clinical setting. In the study by Asano et al. , 1large volume changes must have occurred (the volume infused in dogs by Asano et al.  1corresponds to approximately 6 l within 25 min in a 70-kg human), and we think that these were accompanied by major changes in the strong ion difference and the amount of weak plasma acid, too. Unfortunately, the question whether these changes could completely explain the observed metabolic acidosis according to the Stewart model cannot be answered because no concentrations of electrolytes or plasma protein were presented.

Regarding Dr. Roth’s questions, we do not have a final answer for any of them.

  • 1. We believe that also in dilutional acidosis, a decrease in pH below 7.2 may be harmful because cardiac contractility might be compromised. 5–7This generally implies a therapy of dilutional acidosis when base excess decreases below −10 mm.

  • 2. The maximum degree of dilutional acidosis is not known to us. Obviously, it is not recommended to generate pH values below 7.2, and our experience shows that the pH value can decrease below 7.2 by infusing large amounts of saline. In the investigation by Scheingraber et al. , 8there was a clearly dose-dependent relation between the volume of saline administered and respective changes in pH.

  • 3. We have not yet investigated systematically the time span in which dilutional acidosis usually will be corrected after discontinuation of saline infusion. Probably, it is a matter of several hours, and possibly, this could take longer in patients with renal dysfunctions.

  • 4. Especially in the postoperative period, we frequently see a mixed acidosis of a metabolic acidosis caused by infusion and of a respiratory acidosis due to alveolar hypoventilation caused by anesthetic agents. Therefore, an intraoperatively generated moderate dilutional metabolic acidosis with a base excess below −7 mm, for example, may quickly result in postoperative pH values below 7.2 when arterial carbon dioxide tension exceeds 50 mmHg. As a consequence, we usually perform intraoperatively an alkali therapy at base excess values below −5 mm.

  • 5. Whether in this case sodium bicarbonate or THAM is preferable is currently being investigated in our laboratory.


Asano S, Kato E, Yamauchi M, Ozawa Y, Iwasa M, Wada T, Hasegawa H: The mechanism of the acidosis caused by infusion of saline solution. Lancet 1966; 1: 1245–6
Stewart PA: Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 1983; 61: 1444–61
Sigaard-Andersen O: The Acid-Base Status of the Blood, 4th edition. Copenhagen, Munksgaard, 1976, and Baltimore, Williams & Wilkins, 1976
Scheingraber S, Heitmann L, Weber W, Finsterer U: Are there acid base changes during transurethral resection of the prostate (TURP)? Anesth Analg 2000; 90: 946–50
Mitchell JH, Wildenthal K, Johnson RL: The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Int 1972; 1: 375–89
Williamson JR, Safer B, Rich T, Schaffer S, Kobayashi K: Effects of acidosis on myocardial contractility and metabolism. Acta Med Scand 1976; 199 (suppl 587): 95–112
Shapiro JI: Pathogenesis of cardiac dysfunction during metabolic acidosis: Therapeutic implications. Kidney Int 1997; 51 (suppl 61): 47–51
Scheingraber S, Rehm M, Sehmisch C, Finsterer U: Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. A nesthesiology 1999; 90: 1265–70