review article in the New England Journal of Medicine indicates that the most accurate and straightforward way to assess acid-base disturbances is through a physiological approach. NEJM has begun a series of review articles on acid-base disturbances and management of fluids and electrolytes. There are three ways to quantify acid-base disorders: base-excess, physicochemical, and physiological approaches.

The first study in the NEJM series evaluates the physiological approach—a method based on the carbonic acid-bicarbonate buffer system.

“Based on the isohydric principle, this system characterizes acids as hydrogen-ion donors and bases as hydrogen-ion acceptors. The carbonic acid–bicarbonate system is important in maintaining homeostatic control. In the physiological approach, a primary change in the partial pressure of carbon dioxide (PCO2) causes a secondary ‘adaptive’ response in the bicarbonate concentration and vice versa; further changes in carbon dioxide or bicarbonate reflect additional changes in acid–base status,” according to the NEJM article.

The article outlines five steps a physiological approach uses to assess an acid-base disorder. The first is a thorough clinical evaluation that may indicate the underlying causes of this disorder.

The second step is to assess the primary acid-base disorder and the secondary response. Currently, four recognized primary acid-base disorders exist: two metabolic disorders for acidosis and alkalosis and two respiratory disorders for acidosis and alkalosis. “In response to metabolic acid-base disturbances, changes in the respiratory rate develop quickly, and a new steady-state Paco2 [partial pressure of arterial carbon dioxide] is reached within hours. In cases of persistent respiratory abnormalities, metabolic compensation develops slowly, and 2 to 5 days are required for the plasma bicarbonate concentration to reach a new steady-state level,” the article says.

The third step is to evaluate an acid-base disorder’s metabolic components. “Calculation of the anion gap is useful in the initial evaluation of metabolic acidosis,” according to the NEJMarticle. The fourth looks for the presence of mixed metabolic acid-base disturbances.

A final step in this approach “is to note the serum osmolal gap in any patient with an unexplained high anion gap acidosis, coma, or suspicion of ingestion of a (toxic) alcohol and in hospitalized patients with an increased risk of iatrogenic propylene glycol intoxication,” the article states.

The article mentions three case studies in which the physiological approach was used to evaluate patients with acid-base disorders. The NEJM plans to post online new cases prior to the publication of the next article in the series.​

Authors of the study acknowledge that no ideal means of evaluating acid-base disorders currently exist. Base excess and physicochemical methods each have their limitations. From the authors’ perspective, the physiological approach “remains the simplest, most rigorous, and most serviceable approach to the assessment of acid-base disorders,” the article indicates.