Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019

Abstract Background The management of COVID‐19 ARDS is debated. Although current evidence does not suggest an atypical acute respiratory distress syndrome (ARDS), the physiological response to prone positioning is not fully understood and it is unclear which patients benefit. We aimed to determine whether proning increases oxygenation and to evaluate responders. Methods This case series from a single, tertiary university hospital includes all mechanically ventilated patients with COVID‐19 and proning between 17 March 2020 and 19 May 2020. The primary measure was change in PaO2:FiO2. Results Forty‐four patients, 32 males/12 females, were treated with proning for a total of 138 sessions, with median (range) two (1‐8) sessions. Median (IQR) time for the five sessions was 14 (12‐17) hours. In the first session, median (IQR) PaO2:FiO2 increased from 104 (86‐122) to 161 (127‐207) mm Hg (P < .001). 36/44 patients (82%) improved in PaO2:FiO2, with a significant increase in PaO2:FiO2 in the first three sessions. Median (IQR) FiO2 decreased from 0.7 (0.6‐0.8) to 0.5 (0.35‐0.6) (<0.001). A significant decrease occurred in the first three sessions. PaO2, tidal volumes, PEEP, mean arterial pressure (MAP), and norepinephrine infusion did not differ. Primarily, patients with PaO2:FiO2 approximately < 120 mm Hg before treatment responded to proning. Age, sex, BMI, or SAPS 3 did not predict success in increasing PaO2:FiO2. Conclusion Proning increased PaO2:FiO2, primarily in patients with PaO2:FiO2 approximately < 120 mm Hg, with a consistency over three sessions. No characteristic was associated with non‐responding, why proning may be considered in most patients. Further study is required to evaluate mortality.

secondary to COVID-19 is challenging and debated. Early reports suggested the likelihood of an atypical pathophysiology to explain the pulmonary and systemic manifestations such as the presence of severe hypoxemia with preserved pulmonary mechanics. 3 Some patients with COVID-19 ARDS present with low PaO 2 :FiO 2 ratios despite preserved compliance, which differs from classic ARDS. 4,5 However, emerging evidence indicate that the respiratory system mechanics of patients with ARDS, with or without COVID-19, are broadly similar, advocating standard evidence-based management for ARDS. 6 Prone positioning is considered as one of the most effective strategies for patients with severe ARDS, 7 with improvement in oxygenation attributed to perfusion redistribution, more homogeneous inflation-ventilation, better lung/thoracic shape mismatch, and improved chest wall elastance. 8 While prone positioning is currently used in up to 76% of mechanically ventilated COVID-19 patients, 2,9 the physiological response to proning has not been evaluated in detail, and it is not fully known whether proning leads to improved PaO 2 :FiO 2 similarly to non-COVID-19 ARDS, or which patients benefit from the treatment. The aims of this case series are to describe the respiratory and circulatory effects of prone positioning in mechanically ventilated patients with COVID-19 ARDS in the ICU, to evaluate which patients may respond to proning, and to investigate whether oxygenation improves after repeated proning.

| ME THODS
We retrospectively reviewed all mechanically ventilated adult patients who were treated with prone positioning in the ICU at Södersjukhuset, a tertiary university hospital, between 17 March 2020 and 19 May 2020. Respiratory parameters were collected at four times: 1 hour before proning, 1 hour after the start of proning, 1 hour before return to supine, and 1 hour after return to supine. Follow-up was conducted at 30 days from first proning to determine how many patients were still admitted to the ICU, discharged from the ICU, or deceased. All continuous data are presented as medians with interquartile range (IQR). The primary endpoint was change in PaO 2 :FiO 2 . A power analysis was not performed due to the novelty of the disease during the observation period. Continuous data were compared using Wilcoxon signed rank test, comparing the times 1 hour before proning and 1 hour before return to supine. Analyses were performed using

| RE SULTS
In this cohort of mechanically ventilated patients in the ICU, we  Table 1.

| D ISCUSS I ON
In this case series of mechanically ventilated COVID-19 ARDS patients, we report that prone positioning had an 82% success rate of increased PaO 2 :FiO 2 , and that the effect was consistent after All patients were proned within 1-2 days after the initiation of mechanical ventilation. Guérin et al proned patients with ARDS who had been mechanically ventilated for less than 36 hours and concluded that early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality. 7 The lung stiffness in ARDS lungs increases during mechanical ventilation, 11 and it is possible that the time factor and ventilator days are of importance also in the proning of COVID-19 patients. This is possibly the explanation to why the first three proning sessions were most successful in improving PaO 2 :FiO 2 , although the effect on mortality remains to be investigated.
Prone positioning may also cause potentially severe complications which should be weighed against the potential benefits of the procedure. The complications we report were higher in facial edemas and lower in airway obstruction compared to a previous study. 12 Given the high complication rate of the procedure and no increase of   ARDS present with a form of injury that, in many aspects, is similar to that of those with ARDS of other origins. 13 In ARDS of other origins, and in the absence of contraindications, prone positioning should be considered in mechanically ventilated patients with lack of a control group remaining in supine position.
No characteristic was associated with non-responding, why proning may be considered in most patients. Further study is required to evaluate mortality.

ACK N OWLED G M ENTS
Departmental funding only. The authors declare no conflict of interest.