Abstract

Introduction: Ventilatory ratio (VR) is a bedside index of impaired ventilation that can be used as a surrogate marker for pulmonary dead space fraction (VD/VT). Vasculopathy is hypothesized to increase VD/VT in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. The purpose of this study was to investigate associations between VR and markers of inflammation in critically ill COVID-ARDS patients. Methods: We conducted a retrospective study of patients admitted to an intensive care unit due to SARS-CoV-2 infection. All subjects required invasive mechanical ventilation and met the Berlin criteria for ARDS. Clinical lab values were collected at two timepoints: 2-8 hours after intubation (T1) and 2-24 hours before tracheostomy (T2). VR was split into high (VR>2) and low (VR< 2) groups. Comparisons were performed using student’s t, Mann-Whitney, and z tests for difference in proportions with ⍺=0.05. Results: Of the 139 subjects enrolled at T1, 67 (48%) had high VR (>2), with an overall mean VR of 2.08. High VR was significantly associated with leukocyte count (WBC) (13.3 vs. 10.6 x10^9/L, p=0.004), and platelet count (284 vs 248 x10^9/L, p=0.003). There was no association between VR status and procalcitonin (p=0.08), d-dimer (p=0.73), fibrinogen (p=0.38), CRP (p=0.22), and ferritin (p=0.33). Since certain markers had non-Gaussian distributions, we determined threshold values. D-dimer over 500 ng/mL was associated with higher VR (2.3 vs. 1.8, p=0.004) and procalcitonin over 0.5 ng/mL was moderately associated with higher VR (2.2 vs 1.9, p=0.052). CRP >181 μg/mL (the median) and ferritin values >1.5x the upper limit of normal were not associated with VR (p=0.30 and p=0.26, respectively). To enrich the dataset, we pooled data from T1 and T2 and treated each as an independent sample. In this pooled analysis, high VR was associated with higher platelet count (282 vs. 253, p=0.046), and higher procalcitonin (3.464 vs. 0.964, p=0.032). There were no significant associations with VR and d-dimer (p=0.88), fibrinogen (p=0.54), CRP (p=0.20), and ferritin (p=0.76) in the pooled data. Conclusions: Ventilatory ratio appears to be associated with higher levels of some inflammatory markers including WBC, platelets, d-dimer, and procalcitonin in COVID-ARDS patients.

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