Ventilation Is Not Depressed in Patients with Hypoxemia and Acute COVID-19 Infection
Authors: Kristina Kairaitis, Piotr Harbut, Goran Hedenstierna, G. Kim Prisk, Catherine E. Farrow, Terence Amis, Peter D. Wagner, Atul Malhotra
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Is Not Depressed in Patients with Hypoxemia and Acute COVID-19 InfectionTo the Editor:Early reports of patients with hypoxemia and coronavirus disease (COVID-19) pneumonia exhibiting little respiratory distress have prompted the suggestion that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a unique respiratory pathophysiology (1).One hypothesis to explain the apparent disconnect between severe hypoxemia and the reported absence of dyspnea is a blunted hypoxic ventilatory response (HVR).We therefore sought to test the hypothesis that patients with hypoxemia and COVID-19 have reduced ventilation compared with healthy control subjects.As part of a cross-sectional study of gas exchange in patients with early COVID-19 pneumonia on presentation to the hospital, we measured mean alveolar partial pressure of CO 2 (PA CO 2 ), which represents the inverse of alveolar ventilation ( _ VA), and related it to the severity of hypoxemia as measured by Pa O 2 .Published healthy subject data relating PA CO 2 to Pa O 2 under normoxic and acute hypoxic conditions (2-4) were used to assess whether _ VA levels of patients with COVID-19 were in the expected range for the severity of hypoxemia, thus inferring the ventilatory response of these patients. MethodsThe protocol was approved by the Swedish Ethical Review Authority (diary no.2020-02966).Subjects.Thirty spontaneously breathing symptomatic patients admitted to Danderyd Hospital, Stockholm, Sweden, who were >18 years of age, had a positive PCR result for COVID-19, and had Sa O 2 levels of ,96% were included.Patients unable to maintain constant VT and breathing frequency over the data collection period (of several breaths) were excluded.All patients gave written informed consent.Protocol.Pa O 2 and Pa CO 2 were measured from an arterial blood sample collected over two or three steady-state breaths while the patient was breathing ambient air.Immediately before collecting the blood sample, exhaled CO 2 concentrations and gas flow were measured at 100 Hz at the mouth (Oxycon Pro; Vyaire Medical [5]), and, after adjustment for analyzer lag, mean PA CO 2 was determined as the average of three separate breaths.Measured Pa O 2 and Pa CO 2 were corrected to body temperature (6), and exhaled gas measurements were also temperature adjusted using the Antoine equation.Data analysis.We calculated the term 40/PA CO 2 (indicating the _ VA relative to that which would be present in the same patient had PA CO 2 been normal at 40 mm Hg).This term, abbreviated to _ VArel, was plotted against Pa O 2 . ResultsData were collected from 22 males and 8 females, aged 23-85 years (mean 6 SD, 50.7 6 15.0 yr).All subjects had mildly symptomatic COVID-19 pneumonia; the majority were tachypneic (respiratory rate, 21.8 6 7.2 breaths/min; range, 9-38), 22 had dyspnea, and most were febrile at the time of testing (body temperature, 38.0 6 1.0 C; range, 36.5-40C).No patient required ICU admission.Exhaled CO 2 was collected between 2 and 100 seconds (mean 6 SD, 35 6 10 s) before the arterial blood gas sample.Pa O 2 ranged from 52.9 to 107.5 mm Hg (mean 6 SD, 72.0 6 12.7 mm Hg), arterial oxygen saturation ranged from 89% to 99% (mean 6 SD, 94 6 2%), Pa CO 2 ranged from 27.8 to 46.8 mm Hg (mean 6 SD, 36.3 6 4.6 mm Hg), and _VArel ranged from 1.1 to 1.7 (mean 6 SD, 1.3 6 0.2).Approximately 50% of patients had _ VArel values that were in broad agreement with normal values (Figure 1).For all remaining patients, _ VArel was greater than expected from the normal data.Most importantly, in no patient was _ VArel lower than that seen in healthy subjects at any Pa O 2 .