Implementation of rules for the estimation of compensatory responses in acid-base analysis: A review and proposal for laboratory practice.

Acid-base homeostasis is essential for cellular and systemic function. Its maintenance requires tightly regulated compensatory mechanisms capable of correcting disturbances that threaten physiological balance, as dysregulation can be life-threatening. When a primary metabolic disturbance occurs and alters bicarbonate concentration (HCO₃), the main compensatory mechanism is a respiratory response that adjusts the partial pressure of carbon dioxide (PCO₂). Conversely, a primary respiratory disturbance, whether acute or chronic, leads to changes in PCO₂, and compensatory response occurs through a metabolic response that modifies HCO₃- levels. Mixed disturbances are also common and may represent a diagnostic challenge in clinical practice. To assess acid-base status, clinical laboratories use blood gas analyzers, which provide information to identify metabolic, respiratory, or mixed disorders. Several formulas are available to estimate the compensatory response according to the primary disturbance. These formulas take into account parameters such as PCO₂, actual bicarbonate (HCO₃-c), and standard base excess, all of which are reported in blood gas analysis. The implementation of expert rules within Laboratory Information Systems or Clinical Decision Support tools, which automatically apply these formulas, could facilitate the evaluation of whether compensatory response is appropriate or if a mixed disorder is present, potentially improving the diagnostic accuracy of blood gas analysis and adding value to laboratory reports. This review summarizes the main approaches described in the literature and proposes a standardized procedure to incorporate the study of compensatory mechanisms into the interpretation of acid-base disorders, with the aim of improving diagnostic accuracy and supporting clinicians in patient management.