Early Physiologic Effects of Prone Positioning in COVID-19 Acute Respiratory Distress Syndrome

Francesco Zarantonello, M.D.; Nicolò Sella, M.D.; Tommaso Pettenuzzo, M.D.; Giulio Andreatta, M.D.; Alvise Calore, M.D.; Denise Dotto, M.D.; Alessandro De Cassai, M.D.; Fiorella Calabrese, M.D.; Annalisa Boscolo, M.D.; Paolo Navalesi, M.D.


Anesthesiology. 2022;137(3):241-252. 

In This Article

Abstract and Introduction


Background: The mechanisms underlying oxygenation improvement after prone positioning in COVID-19 acute respiratory distress syndrome have not been fully elucidated yet. The authors hypothesized that the oxygenation increase with prone positioning is secondary to the improvement of ventilation-perfusion matching.

Methods: In a series of consecutive intubated COVID-19 acute respiratory distress syndrome patients receiving volume-controlled ventilation, the authors prospectively assessed the percent variation of ventilation-perfusion matching by electrical impedance tomography before and 90 min after the first cycle of prone positioning (primary endpoint). The authors also assessed changes in the distribution and homogeneity of lung ventilation and perfusion, lung overdistention and collapse, respiratory system compliance, driving pressure, optimal positive end-expiratory pressure, as assessed by electrical impedance tomography, and the ratio of partial pressure to fraction of inspired oxygen (PaO 2/FIO 2; secondary endpoints). Data are reported as medians [25th to 75th] or percentages.

Results: The authors enrolled 30 consecutive patients, all analyzed without missing data. Compared to the supine position, prone positioning overall improved ventilation-perfusion matching from 58% [43 to 69%] to 68% [56 to 75%] (P = 0.042), with a median difference of 8.0% (95% CI, 0.1 to 16.0%). Dorsal ventilation increased from 39% [31 to 43%] to 52% [44 to 62%] (P < 0.001), while dorsal perfusion did not significantly vary. Prone positioning also reduced lung overdistension from 9% [4 to 11%] to 4% [2 to 6%] (P = 0.025), while it did not significantly affect ventilation and perfusion homogeneity, lung collapse, static respiratory system compliance, driving pressure, and optimal positive end-expiratory pressure. PaO 2/FIO 2 overall improved from 141 [104 to 182] mmHg to 235 [164 to 267] mmHg (P = 0.019). However, 9 (30%) patients were nonresponders, experiencing an increase in PaO 2/FIO 2 less than 20% with respect to baseline.

Conclusions: In COVID-19 acute respiratory distress syndrome patients, prone positioning overall produced an early increase in ventilation-perfusion matching and dorsal ventilation. These effects were, however, heterogeneous among patients.


Patients with novel COVID-19 associated acute respiratory distress syndrome (ARDS), despite sharing some features with non–COVID-19 ARDS,[1–4] may present clinical characteristics not completely explained by the typical ARDS pathophysiologic mechanisms.[5,6] In COVID-19 ARDS, alveolar injury is associated with severe pulmonary vascular disruption and small- and mid-sized pulmonary vessels thrombosis,[7,8] mainly ascribable to the COVID-19 related hypercoagulable state.[9]

Radiologic studies assessing lung ventilation and perfusion by subtraction computed tomography angiography showed a high prevalence of perfusion abnormalities, with hypoperfusion predominantly sited in areas of noninjured lungs, and hyperperfusion in the areas of ground-glass opacities, attributed to local inflammation.[10,11] Using electrical impedance tomography, in a small series of COVID-19 patients with ARDS, Mauri et al. reported a high rate of mismatched lung units, the extent of dead space exceeding that of shunt.[12] The same group had also found, in non–COVID-19 ARDS patients, the greater mismatch to be correlated with higher mortality.[13]

Prone positioning has been extensively used in COVID-19 ARDS. In a series of 1,057 COVID-19 intubated and mechanically ventilated patients, Langer et al. report that 648 patients (61%) received at least one cycle of prone positioning, which was effective in improving oxygenation in the majority of patients for whom data were available, but the underlying mechanisms remain unclear.[14] While in non–COVID-19 ARDS the prone position causes, in general, a more homogenous distribution of ventilation between the dorsal and ventral regions of the lung without significant changes in lung perfusion,[15,16] no definitive data are currently available for COVID-19 ARDS patients.

We previously described the case of one COVID-19 ARDS patient who showed, after only 60 min of prone positioning, improvement of the arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FIO2) associated with enhanced ventilation-perfusion matching.[17] Therefore, we hypothesized that in COVID-19 ARDS, arterial oxygenation increases with prone positioning consequent to an improvement of ventilation-perfusion matching, as suggested by a preliminary anecdotal observation.[17] To confirm this hypothesis, we designed this prospective observational study to evaluate the early response to the first cycle of prone positioning in intubated and mechanically ventilated COVID-19 ARDS patients.