Effect of PEEP decremental on respiratory mechanics, gasses exchanges, pulmonary regional ventilation, and hemodynamics in patients with SARS-Cov-2-associated acute respiratory distress syndrome

Abstract

To the editor: Previous reports of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-related acute respiratory distress syndrome (ARDS) have been highlighting a profound hypoxemia and it is not yet well defined how to set positive end-expiratory pressure (PEEP) in this context [1]. In this report, we describe the effects of two levels of PEEP on lung mechanics using a multimodal approach. Patients with confirmed laboratory SARS-Cov-2 infection and meeting criteria for ARDS according to the Berlin definition [2] were eligible within the 48 h after intubation. Written informed consent was waived due to the observational nature of the study. The local ethic approved the study (N° CER-2020-16). Patients were paralyzed and received lung protective ventilation on volume-controlled ventilation. Effects of PEEP decremental were evaluated at two levels of PEEP, arbitrarily 16 cm H2O and 8 cm H2O. These levels were decided based on previous reports [3, 4]. Measurements were performed after 20 min after changing the level of PEEP. Lung mechanics were assessed using an esophageal catheter (NutriVentTM, Italy) [5]. Hemodynamics, indexed extravascular lung water (EVLWi), pulmonary vascular permeability index (PVPI), and cardiac function index (CFI) were monitored by transpulmonary thermodilution (TPTD) device (PiCCO2, Pulsion Medical Systems, Germany). Pulmonary regional ventilation was monitored by the use of an EIT belt placed around the patient’s chest (PulmoVista500; Dräger Medical GmbH Lübeck, Germany) [6]. Ten patients were enrolled and the effects of two levels of PEEP decremental are displayed in Table 1. The PEEP decremental significantly increased both cardiac index and cardiac function index but did not significantly influence other TPTD-related variables. PEEP decremental was not associated with significant changes in gasses exchanges but was associated with a significant decrease in plateau pressure and driving pressure and with a significant decrease in end-inspiratory and in end-expiratory transpulmonary pressures. Lung compliance was significantly higher at low PEEP. Regarding pulmonary regional ventilation, PEEP decremental resulted in a loss of lung impedance associated with a decrease in dorsal fraction. By contrast, decreasing PEEP did not affect global inhomogeneity index. Best PEEP according to the lowest relative alveolar collapse and overdistension was 12 [11–13] cm H2O. Table 1 Changes in hemodynamics, gasses exchanges, respiratory mechanics, and pulmonary regional ventilation between high and low PEEP in supine (n = 10) High PEEP Low PEEP P Clinical variables  Heart rate, beats min−1 72 [64–95] 76 [59–97] 0.977  Systolic arterial blood pressure, mmHg 125 [108–138] 129 [118–140] 0.555  Diastolic arterial blood pressure, mmHg 63 [49–69] 58 [48–65] 0.158  Mean arterial blood pressure, mmHg 77 [72–89] 77 [73–86] > 0.999 Transpulmonary thermodilution indices  Cardiac index, L min−1 m−2 2.5 [2.0–3.0] 2.6 [2.2–3.3] 0.027  Global end-diastolic volume indexed, mL m−2 661 [551–870] 668 [559–813] 0.432  Extravascular lung water, mL kg−1 15 [13–18] 14 [13–17] 0.551  Pulmonary vascular permeability index 3.3 [2.7–3.9] 3.3 [2.7–3.6] 0.607  Cardiac function index, min−1 4.4 [2.4–5.3] 4.5 [2.8–5.8] 0.008 Gas exchanges  pH 7.35 [7.29–7.37] 7.35 [7.30–7.41] 0.305  PaCO2, mmHg 45 [39–51] 44 [40–47] 0.191  PaO2/FiO2 ratio, mmHg 116 [99–196] 106 [86–129] 0.127  SaO2, % 97 [95–98] 96 [92–97] 0.172   V D/V T 0.34 [0.29–0.39] 0.35 [0.30–0.39] 0.348  A-a gradient, mmHg 374 [304–533] 384 [275–543] 0.139 Respiratory mechanics  Respiratory rate, breaths min−1 27 [23–30] 27 [23–30] –  Tidal volume, mL kg−1 IBW 6.0 [6.0–6.3] 6.0 [6.0–6.3] –  Positive end-expiratory pressure, cm H2O 16 [16–16] 8 [8–8] 0.016  Peak pressure, cm H2O 44 [42–47] 35 [33–36] 0.002  Plateau pressure, cm H2O 28 [27–31] 20 [18–21] 0.002  Driving pressure, cm H2O 14 [11–16] 12 [10–13] 0.004  End-expiratory transpulmonary pressure, cm H2O 6 [4–8] 2 [− 1–4] 0.002  End-inspiratory transpulmonary pressure, cm H2O 14 [13–17] 9 [6–10] 0.002  Respiratory system compliance, ml cm H2O−1 29 [27–36] 34 [30–42] 0.012  Respiratory system resistance, cm H2O L−1 s−1 0.24 [0.20–0.25] 0.23 [0.22–0.26] > 0.999  Lung compliance, ml cm H2O−1 47 [40–56] 64 [46–82] 0.008  R/I ratio 0.33 [0.21–0.54] –  End-expiratory lung volume, mL 2546 [2151–3019] 1725 [1450–2023] 0.002 Electrical impedance tomography derived indices  Dorsal fraction, % 46 [43–54] 35 [32–39] 0.002  Global inhomogeneity index, % 58 [52–60] 60 [55–66] 0.059  End-expiratory lung impedance 251 [179–404] 139 [83–243] 0.008  Changes in end-expiratory lung impedance, % −118 [− 150 to − 32] 0.004 Data are presented as median [interquartile range] or number (percentage). Wilcoxon matched pairs signed-rank test was used to evaluate differences between the median values of paired data. PaCO2 partial pressure of arterial carbon dioxide, PaO2 partial pressure of oxygen, FiO2 fraction of inspired oxygen, SaO 2 oxygen saturation, V D /V T estimated dead space fraction, A-a gradient alveolar-arterial gradient, R/I recruitment to inflation ratio. P values refer to the comparison between high and low PEEP for each patient These findings suggest that mechanically ventilated SARS-Cov-2 patients have a relatively preserved lung compliance and that the use of high PEEP was associated with a decrease in lung compliance while providing no beneficial effect on gasses exchanges. Dorsal part of the lung partially collapsed at low PEEP compared to high PEEP. It may suggest that our patients needed a level of PEEP greater than 8 cm H2O. This was actually confirmed by the EIT PEEP titration maneuver. Otherwise, it is interesting to point out that the “best PEEP” according to EIT (12 cm H2O) was close to PEEP set by the clinicians (14 [11–16] cm H2O). Whether larger tidal volumes would have mitigated the dorsal lungs collapse remains speculative and will have to be tested in further studies. This suggests that the increase in lung volume at high PEEP was more likely the result of overdistension of non-dependent part of the lungs than a recruitment of dependent ones (Fig. 1). This interpretation is reinforced by the GI which remained unchanged, indicating stability in the inhomogeneous distribution of ventilation throughout the lungs. Fig. 1 Regional ventilation measured by electrical impedance tomography at low PEEP. Change in topographic distribution of tidal ventilation after a decremental PEEP. Blue areas show a gain in ventilation, and red areas show a loss of ventilation. Right side of the patient is to the left of the image. Back side of the patient is to the bottom of the image This study is the first to describe a multimodal approach of SARS-Cov-2-related ARDS but the findings are limited by the small sample size and the early timing of the evaluation. In conclusion, this series of SARS-Cov-2-related ARDS describe an individualized multimodal approach of lung mechanics, gasses exchanges, pulmonary regional ventilation, and hemodynamics at the early phase of the disease and suggest that low PEEP should be used as part of the ventilation strategy, rather than high PEEP.