Correspondence  |   October 1997
Mechanism of Hyperchloremic Nonanion Gap Acidosis 
Author Notes
  • Chairman, Department of Anesthesiology; Orange Coast Memorial Medical Center; Fountain Valley, California (Miller).
  • Assistant Clinical Professor; Department of Anesthesiology; University of California, Irvine; Orange, California (Waters).
  • (Accepted for publication May 21, 1997.)
Article Information
Correspondence   |   October 1997
Mechanism of Hyperchloremic Nonanion Gap Acidosis 
Anesthesiology 10 1997, Vol.87, 1009-1010. doi:
Anesthesiology 10 1997, Vol.87, 1009-1010. doi:
To the Editor:-We read with great interest the case report, “Dilutional Acidosis: Is It a Real Clinical Entity?”[1 ] Although we praise the authors for their recognition of the development of an unusual metabolic acidosis during this surgical procedure, we question their explanation for the generated acidosis. They pointed out that their patient was persistently hypovolemic and state that, “dilutional acidosis can occur in the presence of intravascular volume depletion.” By definition, dilutional acidosis occurs with volume expansion. It is this volume expansion that results in dilution of plasma bicarbonate and generation of the metabolic acidosis. This acidosis is maintained because of the effects of volume expansion on the ability of the proximal tubules to handle bicarbonate. The increased filtrate across the proximal tubules as a result of volume expansion overwhelms the proximal tubule's ability to reabsorb bicarbonate, and bicarbonaturia results. [2 ] Without this volume expansion, this classic explanation for the mechanism responsible for dilutional acidosis does not work, and another cause for the normal anion gap hyperchloremic metabolic acidosis should be explored.
We, too, have recognized that the development of a hyperchloremic metabolic acidosis is common in patients undergoing surgical procedures with large fluid shifts. In 12 patients, we found no significant decrease in tissue oxygen delivery or increased lactic acid concentrations during the course of the operative procedure. Similar to Mathes' one patient, we found no evidence of volume expansion either by direct plasma volume measurements or pulmonary artery pressure monitoring. Therefore, we were unable to explain the development of the nonanion gap hyperchloremic acidosis by the development of a dilutional acidosis. It was only when we considered the Stewart approach to acid-base balance that we were able to propose a mechanism for this hyperchloremic acidosis. [3 ]
Stewart's approach is a mathematically based model of acid-base balance where the independent variables affecting [H sup +] are clearly determined. [4 ] These variables are the pCO2, the albumin concentration, and the strong ion difference (SID). Of these independent variables, the SID is the most important in determining the final pH of body fluids. [5 ] The SID is the difference between the strong cations (Na sup +,K sup +) and the strong anions (Cl sup -, lactic acid). Strong electrolytes are molecules that completely dissociate when in water, examples being HCl and NaOH. In a solution containing any collection of strong electrolytes, the [H sup +] is determined by the difference between the positively charged and the negatively charged strong ions. To satisfy the law of electroneutrality, any difference in the strong ions should be balanced by changes in [H sup +] or [OH sup -]. A decrease in SID is associated with acidosis, and an increase in SID is associated with alkalosis.
The most dramatic finding among our patients was the development of a highly significant hyperchloremia and a decrease in SID during the course of these prolonged operations. We suggest that the hyperchloremic acidosis consistently observed in these patients undergoing prolonged surgical procedures is related to the chloride load inherent in the intravenous fluid (normal saline) they received. In this case report, the patient received 20 l of normal saline solution intraoperatively. We admit that the literature concerning hyperchloremic metabolic acidosis after saline infusion is relatively sparse, [6–8 ] although reports of hyperchloremic acidosis with the use of hypertonic saline for volume resuscitation would support this hypothesis. [9–10 ] We have observed this hyperchloremic acidosis in virtually every patient who undergoes large fluid shift procedures where large volumes of normal saline solution are administered.
Some anesthesiologists interpret intraoperative acidosis to represent hypovolemia, tissue hypoperfusion, and lactic acidosis. The common practice of chasing this acidosis with more fluid may be worsening the acidosis rather than correcting it. Metabolic acidosis can impair cardiovascular function and lead to hemodynamic instability. [11 ] The clinical challenge that metabolic acidosis poses is more crucial as the dangers of NaHCO3treatment are appreciated. [12,13 ] We urge the anesthesia community to consider Stewart's new approach to acid-base management and consider the importance of changes in [Cl sup -] and in strong ion difference. Understanding of these concepts may lead to different practices of volume replacement during prolonged surgical procedures and an improved acid-base condition of our patients.
Lawrence R. Miller, M.D.
Chairman, Department of Anesthesiology; Orange Coast Memorial Medical Center; Fountain Valley, California
Jonathan H. Waters, M.D.
Assistant Clinical Professor; Department of Anesthesiology; University of California, Irvine; Orange, California
Mathes DD, Morell RC, Rohr MS: Dilutional acidosis: Is it a real clinical entity? Anesthesiology 1997; 86:501-3.
Garella S, Chang BS, Kahn SI: Dilutional acidosis and contraction alkalosis. A review of a concept. Kidney Int 1975; 8:279-83.
Stewart PA: How to Understand Acid-Base. A Quantitative Acid-Base Primer for Biology and Medicine. New York: Elsevier North Holland Inc, 1981.
Stewart PA: Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 1983; 61:1444-61.
Gilfix BM, Bique M, Magder S: A physical chemical approach to the analysis of acid-base balance in the clinical setting. J Crit Care 1993; 4:187-97.
Coran AG, Ballantine TV, Horwitz DL, Herman CM: The effect of crystalloid resuscitation in hemorrhagic shock on acid-base balance: A comparison between normal saline and ringer's lactate solutions. Surgery 1971; 69:874-80.
Rosenbaum BJ, Makoff DL, Maxwell MH: Acid-base and electrolyte changes induced by acute isotonic infusion in the nephrectomized dog. J Lab Clin Med 1969; 74:427-35.
McFarlane C, Lee A: A comparison of Plasmalyte 148 and 0.9% saline for intraoperative fluid replacement. Anaesthesia 1994; 49:779-81.
Vassar MJ, Perry CA, Holcroft JW: Analysis of potential risks associated with 7.5% sodium chloride resuscitation of traumatic shock. Arch Surg 1990; 125:1309-15.
Moon PF, Kramer GC: Hypertonic saline-dextran resuscitation from hemorrhagic shock induces transient mixed acidosis. Crit Care Med 1995; 23:323-31.
Mitchell JH, Wildenthal K, Johnson RL: The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Int 1972; 1:375-89.
Hazard PB, Griffen JP: Sodium bicarbonate in the management of systemic acidosis. South Med J 1980; 73:1339-42.
Graf H, Leach W, Arieff AL: Metabolic effects of sodium bicarbonate in hypoxic lactic acidosis in dogs. Am J Physiol 1985; 249:F630-5.