Evaluation of PEEP and prone positioning in early COVID-19 ARDS

Abstract

Background: In face of the Coronavirus Disease (COVID)-19 pandemic, best practice for mechanical ventilation in COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) is intensely debated. Specifically, the rationale for high positive end-expiratory pressure (PEEP) and prone positioning in early COVID-19 ARDS has been questioned.

Methods: The first 23 consecutive patients with COVID-19 associated respiratory failure transferred to a single ICU were assessed. Eight were excluded: five were not invasively ventilated and three received veno-venous ECMO support. The remaining 15 were assessed over the first 15 days of mechanical ventilation. Best PEEP was defined by maximal oxygenation and was determined by structured decremental PEEP trials comprising the monitoring of oxygenation, airway pressures and trans-pulmonary pressures. In nine patients the impact of prone positioning on oxygenation was investigated. Additionally, the effects of high PEEP and prone positioning on pulmonary opacities in serial chest x-rays were determined by applying a semiquantitative scoring-system. This investigation is part of the prospective observational PA-COVID-19 study.

Findings: Patients responded to initiation of invasive high PEEP ventilation with markedly improved oxygenation, which was accompanied by reduced pulmonary opacities within 6 h of mechanical ventilation. Decremental PEEP trials confirmed the need for high PEEP (17.9 (SD ± 3.9) mbar) for optimal oxygenation, while driving pressures remained low. Prone positioning substantially increased oxygenation (p<0.01).

Interpretation: In early COVID-19 ARDS, substantial PEEP values were required for optimizing oxygenation. Pulmonary opacities resolved during mechanical ventilation with high PEEP suggesting recruitment of lung volume.

Funding: German Research Foundation, German Federal Ministry of Education and Research.

Fig. 1

Study cohort flowchart. A, The first consecutive 23 COVID-19 patients treated on our ICU were enrolled to this study, investigating PEEP and prone positioning in mechanically ventilated patients. Eight patients were excluded from the assessment of the specific interventions as they received ECMO therapy (three patients, ECMO therapy would interfere with the analysis of oxygenation), or high-flow oxygen therapy but no mechanical ventilation (five patients that could not be asses regarding the effects of invasive mechanical ventilation, PEEP and prone positioning), resulting in 15 patients eligible for this study. Ten patients were intubated in our ICU (Subset 1, intubation group), while eight patients were transferred intubated to our ward. For seven of the 15 mechanically ventilated patients, a full dataset of decremental PEEP trials was available and they were accordingly included in Subset 2 (PEEP trial analysis) for determination of optimal PEEP. Nine of the fifteen patients were subject to prone positioning (Subset 3, prone position analysis). B, Illustration of the allocation of the 15 patients to each analysis.

Fig. 2

Invasive positive pressure ventilation with high PEEP improves oxygenation and reduces opacities in chest x-rays. The left boxplots (A) present the P_aO₂/F_iO₂ ratio two hours prior and six hours post intubation from the ten patients of Subset 1. Scoring of pulmonary opacities was performed, showing a reduction in pulmonary opacity scores with positive pressure ventilation (B). Representative chest x-ray images of one patient obtained before intubation (C) and after onset of mechanical ventilation (D) are shown. Whiskers indicate the 5th and 95th percentile. The cross within the box marks the mean. A two-sided paired t-test (A), and a Wilcoxon signed-rank test (B) was performed. **p<0·01, ***p<0·001.

Fig. 3

Prone positioning improves oxygenation. P_aO₂/F_iO₂ ratio was measured in nine patients subjected to prone positioning (Subset 3). Group data show P_aO₂/F_iO₂ ratio after the first prone positioning (PP) relative to the previous supine position (SP) (A), after the first three PP maneuvers vs. the three preceding SPs (B), and for all prone positions (C). Whiskers indicate the 5th and 95th percentile. The cross within the box marks the mean. A two-sided paired t-test was performed. *p<0·05, **p<0·01.