Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units

Abstract

Background: COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients.

Methods: This is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO₂) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO₂ parameters: deoxygenation rate (DeO₂), reoxygenation rate (ReO₂), and hyperemic response (H_AUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO₂) and the fraction of inspired oxygen (FiO₂) (SF ratio).

Results: Healthy controls (32) and COVID-19 patients (73) were studied. Baseline StO₂ and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO₂) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO₂ and DeO₂ negatively correlated with SF ratio, while ReO₂ showed a positive correlation with SF ratio. There were significant differences in baseline StO₂ and ReO₂ among the different ARDS groups according to SF ratio, but not among different respiratory support therapies.

Conclusion: Patients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial. Trial registration ClinicalTrials.gov NCT04689477 . Retrospectively registered 30 December 2020.

Keywords: COVID-19; Endothelial dysfunction; Microcirculation; Near-infrared spectroscopy.

Fig. 1

Box-plot and individual data points showing microcirculatory parameters in healthy volunteers and COVID-19 patients. Although baseline StO₂ values did not differ, all dynamic StO₂ indices were altered in COVID-19 patients, as compared to healthy controls

Fig. 2

Box-plot and individual data points showing microcirculatory alterations in IRCU/ICU patients according to respiratory support. The distribution of StO₂ parameters did not differ when categorizing the patients according to receiving invasive mechanical ventilation (53%) or non-invasive respiratory support (47%). The most frequent non-invasive support was high-flow nasal cannula (32%), followed by Venturi mask (11%), and non-invasive mechanical ventilation (4%)

Fig. 3

Box-plot and individual data points showing microcirculatory alterations in IRCU/ICU patients according to the severity of ARDS. The distribution of StO₂ and ReO₂ was significantly different among patients according to the severity of ARDS. A post hoc Tukey comparison showed that severe ARDS patients had higher StO₂ values as compared to moderate ARDS, and lower ReO₂ values, as compared to mild ARDS. The distribution of DeO₂ among groups did not reach statistical significance (p = 0.053)