Has Stewart approach improved our ability to diagnose acid-base disorders in critically ill patients?

Abstract

The Stewart approach-the application of basic physical-chemical principles of aqueous solutions to blood-is an appealing method for analyzing acid-base disorders. These principles mainly dictate that pH is determined by three independent variables, which change primarily and independently of one other. In blood plasma in vivo these variables are: (1) the PCO2; (2) the strong ion difference (SID)-the difference between the sums of all the strong (i.e., fully dissociated, chemically nonreacting) cations and all the strong anions; and (3) the nonvolatile weak acids (Atot). Accordingly, the pH and the bicarbonate levels (dependent variables) are only altered when one or more of the independent variables change. Moreover, the source of H(+) is the dissociation of water to maintain electroneutrality when the independent variables are modified. The basic principles of the Stewart approach in blood, however, have been challenged in different ways. First, the presumed independent variables are actually interdependent as occurs in situations such as: (1) the Hamburger effect (a chloride shift when CO2 is added to venous blood from the tissues); (2) the loss of Donnan equilibrium (a chloride shift from the interstitium to the intravascular compartment to balance the decrease of Atot secondary to capillary leak; and (3) the compensatory response to a primary disturbance in either independent variable. Second, the concept of water dissociation in response to changes in SID is controversial and lacks experimental evidence. In addition, the Stewart approach is not better than the conventional method for understanding acid-base disorders such as hyperchloremic metabolic acidosis secondary to a chloride-rich-fluid load. Finally, several attempts were performed to demonstrate the clinical superiority of the Stewart approach. These studies, however, have severe methodological drawbacks. In contrast, the largest study on this issue indicated the interchangeability of the Stewart and conventional methods. Although the introduction of the Stewart approach was a new insight into acid-base physiology, the method has not significantly improved our ability to understand, diagnose, and treat acid-base alterations in critically ill patients.

Keywords: Acid-base metabolism; Anion gap; Base excess; Bicarbonate; Stewart approach; Strong ion difference; Strong ion gap.

Figure 1

Independent determinants of pH according to the Stewart approach.

Figure 2

Behavior of pH (top), HCO₃^- (middle) and PCO₂ (bottom) in a closed system (black dots) and in an open system with a PCO₂ of 40 mmHg (withe dots), during stepwise dilution with 0.9% NaCl, as modified from Gattinoni et al[32].

Figure 3

Regression and Bland and Altman analysis between metabolic parameters of different approaches in seven normal volunteers. A: Lineal regression between base excess and strong ion difference; B: Agreement between base excess and strong ion difference; C: Lineal regression between albumin-corrected anion gap and strong ion gap; D: Agreement between albumin-corrected anion gap and strong ion gap; Panel B and D display the relationship between the mean value and the difference of both measurements. The lines indicate the mean difference between both parameters (bias) ± 2 SD (95% limits of agreement). Modified from Dubin et al[37].

Figure 4

Regression and Bland and Altman analysis between metabolic parameters of different approaches in 935 critically ill patients. A: Lineal regression between base excess and strong ion difference; B: Agreement between base excess and strong ion difference; C: Lineal regression between albumin-corrected anion gap and strong ion gap; D: Agreement between albumin-corrected anion gap and strong ion gap. Panel B and D display the relationship between the mean value and the difference between both measurements. The lines indicate the mean difference between both parameters (bias) ± 2 SD (95% limits of agreement). Modified from Dubin et al[37].

Figure 5

Arterial pH, and bicarbonate levels in patients with severe hyperlactatemia. Values for (A) arterial pH, (B) PCO₂, and (C) bicarbonate ([HCO₃^-]) in patients with severe hyperlactatemia, with normal or low base excess. ^aP < 0.05 vs the other group.

Figure 6

Strong-ion difference, sodium-corrected chloride, albumin, and nonvolatile weak acid levels in severe hyperlactatemia patients. Values for (A) the effective strong-ion difference (SID_effective), (B) sodium-corrected chloride levels (Cl^-_corrected), (C) the albumin concentration, and (D) nonvolatile weak acid (Atot) levels in patients with severe hyperlactatemia, with normal or low base excess. ^aP < 0.05 vs the other group. SID_effective: Effective strong-ion difference.