Prone Position in Intubated, Mechanically Ventilated Patients With COVID-19

A Multi-Centric Study of More Than 1000 Patients

Thomas Langer; Matteo Brioni; Amedeo Guzzardella; Eleonora Carlesso; Luca Cabrini; Gianpaolo Castelli; Francesca Dalla Corte; Edoardo De Robertis; Martina Favarato; Andrea Forastieri; Clarissa Forlini; Massimo Girardis; Domenico Luca Grieco; Lucia Mirabella; Valentina Noseda; Paola Previtali; Alessandro Protti; Roberto Rona; Francesca Tardini; Tommaso Tonetti; Fabio Zannoni; Massimo Antonelli; Giuseppe Foti; Marco Ranieri; Antonio Pesenti; Roberto Fumagalli; Giacomo Grasselli


Crit Care. 2021;25(128) 

In This Article


In this national, multicentre, retrospective observational study performed in the ICUs of 24 Italian hospitals during the first peak of the 2020 COVID-19 pandemic, we investigated the use of prone positioning in a cohort of 1057 critically ill, invasively ventilated patients with respiratory failure due to COVID-19. We also analyzed the pathophysiologic respiratory effects of this manoeuvre in a subset of 78 patients. A major finding of our study is that prone positioning was applied very frequently, significantly more often than previously reported in other populations of ARDS patients.[28,29] Indeed, 61% of our patients underwent at least one pronation session during their ICU stay, as compared to 8% of the patients enrolled in the LUNG SAFE study. The frequency of use of prone positioning increased with increasing ARDS severity. Notably, 77% of COVID-19 patients with severe ARDS underwent prone positioning, as compared to the 16% of those with severe ARDS in the LUNG SAFE cohort. Of note, prone position was also frequently applied in patients with mild and moderate ARDS at ICU admission.

Changing body position from supine to prone (or vice versa) requires dedicated and experienced personnel. Moreover, the manoeuvre frequently requires incremental dosages of sedatives and muscle relaxants[30] and may lead to hemodynamic instability. In addition, it is associated with an increased risk of device displacement and pressure ulcers.[31] It is important to underline that in our study, the decision to turn the patients in prone position was at the discretion of the ICU team, i.e. there were no pre-specified criteria for the application of this rescue manoeuvre. Due the overwhelming number of critically ill patients requiring ICU admission, the ICU bed capacity of our hospitals had to be rapidly increased.[32] Therefore, many physicians and nurses usually working outside the ICU environment and even doctors from other specialities were recruited to allow the surge in ICU capacity. This of course reduced the expertise of the whole ICU staff. Our data clearly show that prone positioning was applied to patients with more severe disease, mainly as a rescue therapy (Table 1). Consequently, the worse clinical outcomes of patients undergoing prone positioning can be explained by the higher disease severity. However, given the retrospective nature of the study, we cannot draw any conclusions on the efficacy of prone position in terms of outcome.

Another important finding, resulting from the physiological sub-study, is that, on average, the PaO2/FiO2 ratio increased significantly from 98 [72–212] to 158 [112–220] mmHg, p < 0.001 (Figure 1b) during the first pronation session. Moreover, while the PaO2/FiO2 ratio dropped with re-supination, as previously observed,[33,34] values after re-supination remained significantly higher than baseline values (128 [87–174] vs. 98 [72–212], p < 0.05).

The findings of the physiologic sub-study (Table 2) thus suggest that the main mechanism inducing an improvement in oxygenation during the first pronation of COVID-19 patients with ARDS is the improvement of the ventilation-perfusion matching, possibly favoured by a redistribution of flow from dorsal to ventral lung areas. Indeed, the lack of improvement of respiratory system compliance with the change in body position (Figure 1a) suggests that lung recruitment was not the major mechanism. This hypothesis is also suggested by the fact that patients with lower driving pressure/higher respiratory system compliance and thus higher lung volumes, had, on average, greater increases in PaO2/FiO2 ratio (Figure E2). We observed a modest, though significant increase in set respiratory rate and a resulting trend toward higher minute ventilations during prone positioning (Table 2). However, we did not observe a significant variation of the ventilatory ratio, a proxy of dead space and efficiency in CO2 removal (Figure 1c). Taken together, these results suggest that CO2 production somehow increased during prone position, requiring an increase in minute ventilation to maintain stable PaCO2 values.

We used an increase in PaO2/FiO2 ratio during pronation of at least 20 mmHg as cut-off to define the response to prone position in terms of oxygenation. Using this definition, 78% of the studied patients were considered "O2-Responders". There are no universally applied criteria to define the response to prone position, however, when looking at the literature using the same cut-off,[26,27] the percentage of patients with COVID-19-induced ARDS that responded to prone position seems similar to the percentage of the "general" ARDS population.[26]

When analyzing the differences between O2-Responders and Non-Responders, we observed that, despite similar comorbidities and baseline severity scores, respiratory failure was on average more severe in O2-Non-Responders (Table 3). Indeed, Non-Responders had higher driving pressure and ventilatory ratio, suggesting a higher extension of lung dysfunction and a lower efficiency of gas exchange. In the ARDS literature, several studies did not find a different mortality between Responders and Non-Responders in terms of oxygenation,[26,27] while a recent study performed on ARDS, non-COVID patients, suggested that improved oxygenation after prone positioning might be a predictor of survival.[35] Also in our study performed in COVID-19 ARDS patients, we found that the mortality of O2-Non-Responders was significantly higher as compared to Responders (65% vs. 38%, p = 0.039).

In order to evaluate the response to pronation in terms of CO2 clearance, we analyzed the variations in ventilatory ratio. Also in this case, there is no universally applied criteria to define CO2-Responders, and several cut-offs of absolute changes in partial pressure of CO2 (PCO2) during prone position have been previously used.[26,36–38] The variation in PCO2 is used as a proxy of the efficiency of the system to eliminate CO2, i.e. pulmonary dead space fraction. Of course, this proxy can be evaluated only if the ventilatory settings do not change during prone position and, ideally, if the CO2 production is stable. We recorded a significant increase in respiratory rate and thus minute ventilation during prone position and therefore could not use the variation in PCO2 as a proxy of dead space variation. We therefore used a variation in the ventilatory ratio to differentiate between CO2-Responders and Non-Responders. In this exploratory analysis, CO2-Non-Responders were found to be older and with more comorbidities; however, no significant difference in outcome was observed.


The retrospective observational nature of the study is a clear limitation of our study. As already discussed, the decision to place the patient in prone position was at discretion of the attending physicians and the general clinical patient management was not standardized among centres. The comparison between the two groups gives therefore useful information about the decision-making process of Italian doctors caring for severely ill COVID-patients during the first wave of the 2020 COVID pandemic. On the contrary, the comparison does not provide information about the efficacy of pronation in terms of outcome. In addition, we have not collected information regarding complications related to prone positioning. A certain rate of complications usually occurs during prone position. It is conceivable that the rate might be higher in the specific context of a pandemic surge. Regarding the physiologic sub-study, the absence of information of partitioned respiratory mechanics is certainly a limitation. Nevertheless, the fact that the respiratory system compliance did not change in the 3 time-points suggests that lung recruitment did not play a significant role during the first pronation. Moreover, the limited number of patients included in the physiologic sub-study limits the soundness of the observed differences between Responders and Non-Responders, both in terms of oxygenation and carbon dioxide clearance.