Potential for the lung recruitment and the risk of lung overdistension during 21 days of mechanical ventilation in patients with COVID-19 after noninvasive ventilation failure: the COVID-VENT observational trial

Abstract

Background: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation.

Methods: This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum» positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO₂ and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH₂O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (C_RS), PaO₂/FiO₂, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21.

Results: The «optimum» PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH₂O and 10.0 (9.0-12.0) cmH₂O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH₂O and VT increase by 100 and 200 ml led to a significant decrease in C_RS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7-2,7) in non-survivors and in 1.9 (1.6-2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO₂/FiO₂ was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p = 0.002). In survivors, PaO₂/FiO₂ rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046).

Conclusion: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate» PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched C_RS.

Trial registration: ClinicalTrials.gov, NCT04445961 . Registered 24 June 2020-Retrospectively registered.

Keywords: Acute respiratory distress syndrome; COVID-19; Lung recruitability; Lung strain; PEEP; Volutrauma.

Fig. 1

The study cohort selection

Fig. 2

The driving pressure at different positive end-expiratory pressure levels (PEEP) («PEEP trial») in survivors and non-survivors during 21 days of the mechanical ventilation. A Day 1. B Day 3. C Day 5. D Day 7. E Day 14. F Day 21. Data on survivors (black) and non-survivors (grey) is presented as medians and 95% confidence in-tervals. The x-axis represents positive end-expiratory pressure levels in cmH2O . * p-value < 0.05, comparison within subgroup of survivors and non-survivors (Friedman test) ; ** p-value < 0.01, comparison within subgroup of survivors and non-survivors (Friedman test) ;§ p-value < 0.001, comparison within subgroup of survivors and non-survivors (Friedman test)

Fig. 3

Normalized static compliance at preset tidal volume and during tidal volume increase («volume trial») in survivors and non-survivors during 21 days of the mechanical ventilation. A Day 1. B Day 3. C Day 5. D Day 7. E Day 14. F Day 21. Data on survivors (black) and non-survivors (grey) is presented as medians and 95% confidence in-tervals. The x-axis represents three points: initial tidal volume, tidal volume increased by 100 ml and tidal volume increased by 200 ml. Normalized static compliance calculated dividing the tidal volume in ml/kg of the ideal body weight to driving pressure.* p-value < 0.05, comparison within subgroup of survivors and non-survivors (Friedman test);** p-value < 0.01, comparison within subgroup of survivors and non-survivors (Friedman test);§ p-value < 0.001, comparison within subgroup of survivors and non-survivors (Friedman test)

Fig. 4

The gas exchange, respiratory mechanics and plethysmogram varia-bility during 28 days of the mechanical ventilation in survivors and non-survivors. A PaO2/FiO2. B Ventilatory ratio. C Alveolar dead space to tidal volume ratio. D Static compliance of the respiratory system. E The «optimum» positive end ex-piratory pressure balanced between the lowest driving pressure and the highest pe-ripheral oxygen saturation (SpO2). F Change in plethysmogram variability index during the recruitment maneuver (Days 1 and 7) or the tidal volume increase by 200 ml (on Days 3, 5,10,14, 21 and 28). Data on survivors (black) and non-survivors (grey) is presented as medians and 95% confidence in-tervals. The x-axis represents days after initiation of the mechanical ventilation. Abbreviations: PaO2- partial pressure of oxygen in arterial blood; FiO2—inspiratory oxygen fraction; VDalv—alveolar dead space: VT- tidal volume; PEEP—positive end-expiratory pressure; PVI—ple-thysmogram variability index; SpO2 peripheral oxygen saturation.* p-value < 0.05, comparison between survivors and non-survivors (Mann-Whitney U test) ;** p-value < 0.01, comparison between survivors and non-survivors (Mann-Whitney U test) ;§ p-value < 0.001, comparison between survivors and non-survivors (Mann-Whitney U test)

Fig. 5

The «optimum» positive end-expiratory pressure (PEEP) levels on Day 1 and Day 7 in survivors and non-survivors. Data on Day 1(white) and Day 7 (grey) is presented as medians and 95% confidence intervals.* p-value < 0.05, comparison between Day 1 and Day 7 in subgroups of survivors and non-survivors