Downloaded from http://journals.lww.com/clinpulm by BhDMf5ePHKbH4TTImqenVAaoM33QR5KTFkk7E55VmCDVdnIP9E6mvBCPh9Ke/WGg on 07/03/2020 Bedside Rules for Managing Acid-Base Derangement in Respiratory Failure: Applications to COVID-19 Marco Marano, MD and Luigi Senigalliesi, MD Abstract: Respiratory failure is typically associated with changes in pCO 2 leading to respiratory alkalosis (type 1 failure) and respiratory acidosis (type 2). As a compensatory response, plasma HCO 3 concen- tration decreases if pCO 2 decreases and increases conversely. These secondary responses prevent large pH fluctuations. However, metabolic acid-base disorders may still occur as a consequence of dysfunction of other organs and/or medical treatments. To recognize superimposed acid-base disorders, the availability of an accurate prediction of the expected HCO 3 that corresponds to a given pCO 2 is crucial. In chronic hypocapnia, the compensatory metabolic response is regulated by the equation ΔHCO 3 /ΔpCO 2 = 0.4 mEq/L per mm Hg. An easy rule to compute the expected value of HCO 3 may be 0.4×pCO 2 +9. In chronic hypercapnia, the equation is ΔHCO 3 /ΔpCO 2 = 0.48 mEq/L per mm Hg, and the expected value of HCO 3 becomes 0.48×pCO 2 +4.74. While this expression is accurate, it seems to be of limited use for simple “bedside” predictions. In this contribution, we propose the simpler expression: the expected value of HCO 3 in chronic hypercapnia =½ pCO 2 +3.5. For values of pCO 2 not exceeding 70 mm Hg, with the proposed expression, the difference in HCO 3 prediction in respect to the previous one is < 0.5 mEq/L, which is clinically negligible. The root mean square value of the error introduced by the proposed expression is as small as 0.19 mEq/L. Because of its accuracy, we believe that the proposed formula may be useful to identify mixed disorders at the bedside in a simpler way. Key Words: acid-base, respiratory acidosis, respiratory alkalosis, sec- ondary response (Clin Pulm Med 2020;27:51–53) I nterstitial pneumonia is a typical feature of COVID-19 dis- ease. Because of its fast development and lack of intensive care unit resources, many patients with severe pneumonia have to stay in the general ward for days while experiencing pro- gressive respiratory failure. Nonintensivists have to take care of critically ill patients. A relevant issue is the management of acid-base imbalance associated with pneumonia. Patients suffering with COVID-19 pneumonia may show respiratory conditions ranging from low-grade hypoxemia to acute respiratory distress syndrome. 1 Their alveolar ventilation may increase as a compensatory response to hypoxia but could also remain severely impaired. This means that pCO 2 may vary over a wide range of values. Moreover, metabolic alkalosis and metabolic acidosis can superimpose with respiratory acid-base disorders due to critical conditions. The presence of more than one acid-base disorder at the same time leads to mixed acid- base disorders. In 2 cohorts of Chinese patients, 1,2 the nonsurvivor groups showed values of pCO 2 lower than those of survivors. This leads to the conjecture that respiratory alkalosis was the underlying disorder. However, roughly 75% of deceased patients did not show alkalemic pH, 1 and severe COVID-19 disease also implied lactic acidosis. 2 Thus, mixed disorders were present in severe cases of pneumonia. Although the nosology of simple and mixed disorders is established, several shadows still exist with regard to the magnitude of deviations of acid-base parameters in extreme derangements and in mixed disorders. Respiratory failure occurs if pO 2 drops below the thresh- old of 60 mm Hg. This pO 2 reduction, by itself, should not affect the acid-base equilibrium, unless it is associated with changes in pCO 2 . In type 1 respiratory failure, the alveolar ventilation increases, and this tends to lower CO 2 . In turn, the pCO 2 fall implies an increase in pH eventually causing respi- ratory alkalosis. Conversely, in type 2 respiratory failure, the inadequate alveolar ventilation causes the increase of pCO 2 that triggers a reduction of pH. As a secondary compensatory response to any pCO 2 change, several mechanisms are activated to adapt HCO 3 levels, thus mitigating pH variations. If they are malfunctioning, physicians should support them to sustain myocardial contractility, arterial constriction, and oxygen delivery to tissues, all impaired when the pH falls below 7.1. In these cases, medical interventions should first address respira- tory functions and then the plasma HCO 3 concentration. For a given pCO 2 level, there exist several recipes to predict the associated HCO 3 concentration, which is the so- called expected value resulting by compensatory mechanisms. These rules of thumb quantify the magnitude of secondary response and therefore allow to predict the integrity of com- pensatory pathways if the measured value fits the expected one, and to infer the coexistence of additional acid-base disorders if it does not. The latter case is not rare in patients with severe illness, older age, or multiple comorbidities. The correct diag- nosis and treatment of these disorders improves the patient’s outcome and allows extra time, which is not a minor point in patients’ management. Knowing the expected HCO 3 value may help the clinician to support an impaired physiological function —for example, by the administration of sodium bicarbonate when measured HCO 3 is below the expected value. SECONDARY RESPONSE TO HYPOCAPNIC TYPE 1 RESPIRATORY FAILURE As soon as hypocapnia, that is, respiratory alkalosis, appears, red cells and the chemical buffers release acids to consume HCO 3 and to limit the increase of pH. These secon- dary responses lead to a reduction in serum HCO 3 of 0.2 to 0.4 mEq/L per each mm Hg of decrease in pCO 2 . 3 In hypocapnia that might have a duration lasting from minutes to hours, the expression ΔHCO 3 /ΔpCO 2 = 0.2 mEq/L per mm Hg is fully consistent with the limits of expected response, as defined by From the Unit of Nephrology and Dialysis, Maria Rosaria Clinic, Pompeii, Naples, Italy. Disclosure: The authors declare that they have no conflicts of interest. Address correspondence to: Marco Marano, MD, via Colle San Bartolomeo, 50—Pompeii 80045, Naples, Italy. E-mail: marano965@gmail.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1068-0640/20/2702-0051 DOI: 10.1097/CPM.0000000000000354 CRITICAL CARE/RESPIRATORY CARE Clinical Pulmonary Medicine  Volume 27, Number 2, March 2020 www.clinpulm.com | 51 Copyright r 2020 Wolters Kluwer Health, Inc. All rights reserved.