Heterogeneity of Ventilation/Perfusion Mismatch at Different Levels of PEEP and in Mechanical Phenotypes of COVID-19 ARDS.

BACKGROUND: COVID-19-related ARDS is characterized by severe hypoxemia with initially preserved lung compliance and impaired ventilation/perfusion (V̇/Q̇) matching. PEEP can increase end-expiratory lung volume, but its effect on V̇/Q̇ mismatch in COVID-19-related ARDS is not clear. METHODS: We enrolled intubated and mechanically ventilated subjects with COVID-19 ARDS and used the automatic lung parameter estimator (ALPE) to measure V̇/Q̇. Respiratory mechanics measurements, shunt, and V̇/Q̇ mismatch (low V̇/Q̇ and high V̇/Q̇) were collected at 3 PEEP levels (clinical PEEP = intermediate PEEP, low PEEP [clinical - 50%], and high PEEP [clinical + 50%]). A mixed-effect model was used to evaluate the impact of PEEP on V̇/Q̇. We also investigated if PEEP might have a different effect on V̇/Q̇ mismatch in 2 different respiratory mechanics phenotypes, that is, high elastance/low compliance (phenotype H) and low elastance/high compliance (phenotype L). RESULTS: Seventeen subjects with COVID-related ARDS age 66 [60-71] y with a PaO2 /FIO2 of 141 ± 74 mm Hg were studied at low PEEP = 5.6 ± 2.2 cm H2O, intermediate PEEP = 10.6 ± 3.8 cm H2O, and high PEEP = 15 ± 5 cm H2O. Shunt, low V̇/Q̇, high V̇/Q̇, and alveolar dead space were not significantly influenced, on average, by PEEP. Respiratory system compliance decreased significantly when increasing PEEP without significant variation of PaO2 /FIO2 (P = .26). In the 2 phenotypes, PEEP had opposite effects on shunt, with a decrease in the phenotype L and an increase in phenotype H (P = .048). CONCLUSIONS: In subjects with COVID-related ARDS placed on invasive mechanical ventilation for > 48 h, PEEP had a heterogeneous effect on V̇/Q̇ mismatch and, on average, higher levels were not able to reduce shunt. The subject's compliance could influence the effect of PEEP on V̇/Q̇ mismatch since an increased shunt was observed in subjects with lower compliance, whereas the opposite occurred in those with higher compliance.

Long-term dyspnea, regional ventilation distribution and peripheral lung function in COVID-19 survivors: a 1 year follow up study.

BACKGROUND: Dyspnea is common after COVID-19 pneumonia and can be characterized by a defective CO2 diffusion (DLCO) despite normal pulmonary function tests (PFT). Nevertheless, DLCO impairment tends to normalize at 1 year, with no dyspnea regression. The altered regional distribution of ventilation and a dysfunction of the peripheral lung may characterize dyspnea at 1 year after COVID-19 pneumonia. We aimed at assessing the pattern of airway resistance and inflammation and the regional ventilation inhomogeneity in COVID-19 pneumonia survivors at 12-months after hospital discharge. METHODS: We followed up at 1-year patients previously admitted to the respiratory units (intensive care or sub-intensive care unit) for COVID-19 acute respiratory failure at 1-year after hospital discharge. PFT (spirometry, DLCO), impulse oscillometry (IOS), measurements of the exhaled nitric oxide (FENO) and Electrical Impedance Tomography (EIT) were used to evaluate lung volumes, CO2 diffusion capacity, peripheral lung inflammation/resistances and the regional inhomogeneity of ventilation distribution. A full medical examination was conducted, and symptoms of new onset (not present before COVID-19) were recorded. Patients were therefore divided into two groups based on the presence/absence of dyspnea (defined as mMRC ≥1) compared to evaluate differences in the respiratory function derived parameters. RESULTS: Sixty-seven patients were admitted between October and December 2020. Of them, 42/67 (63%) patients were discharged alive and 33 were evaluated during the follow up. Their mean age was 64 ± 11 years and 24/33 (73%) were males. Their maximum respiratory support was in 7/33 (21%) oxygen, in 4/33 (12%) HFNC, in 14/33 (42%) NIV/CPAP and in 8/33 (24%) invasive mechanical ventilation. During the clinical examination, 15/33 (45%) reported dyspnea. When comparing the two groups, no significant differences were found in PFT, in the peripheral airway inflammation (FENO) or mechanical properties (IOS). However, EIT showed a significantly higher regional inhomogeneity in patients with dyspnea both during resting breathing (0.98[0.96-1] vs 1.1[1-1.1], p = 0.012) and during forced expiration (0.96[0.94-1] vs 1 [0.98-1.1], p = 0.045). CONCLUSIONS: New onset dyspnea characterizes 45% of patients 1 year after COVID-19 pneumonia. In these patients, despite pulmonary function test may be normal, EIT shows a higher regional inhomogeneity both during quiet and forced breathing which may contribute to dyspnea. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT04343053, registration date 13/04/2020.