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


One thousand three hundred twenty-six patients fulfilled the inclusion criteria. After exclusions (one patient aged < 18 years, 123 patients with missing information regarding the use of prone position and 145 patients who were never intubated), 1057 patients were analyzed (Flowchart reported in Additional file 1: Figure E1).

Table 1 summarizes the patients' demographic and clinical characteristics at ICU admission and their clinical outcomes. Additional information is reported in Additional file 1, Table E2. Most patients were male (79%), median age was 63 [55–69] years, and median body mass index was 28 [25–31] kg/m2. Median SAPS II and SOFA score at ICU admission were 36 [30–44] and 4 [3–4], respectively. Eighty-four % of patients were intubated and mechanically ventilated at ICU admission or during the first day in ICU. ARDS severity was mild in 15%, moderate in 50% and severe in 35% of the cases. Median PaO2/FiO2 ratio, respiratory rate, tidal volume/predicted body weight and plateau airway pressure of mechanically ventilated patients were 120 mmHg [88–173], 20 [18–25] breaths/min, 7.0 [6.3–7.8] mL/kg and 24 [22–27] cmH2O, respectively. As of July 15, 2020, 677 (64%) patients had been discharged from the ICU and 374 (36%) had died (6 missing data). Mortality increased significantly with increasing severity of ARDS (25, 33, 41%, p = 0.004, for mild, moderate and severe ARDS, respectively). The median ICU length of stay was 16 [10–28] days for patients discharged from the ICU, and 12 [6–20] days for those who died in the ICU.

Use of Prone Positioning and Differences Between Pronated and Non-pronated Patients

Six-hundred and forty-eight patients (61% of the overall population) were placed in prone position at least once during their stay in the ICU (PP Group), while 409 patients (39% of the overall population) were always treated in the supine position (SP Group). The frequency of use of prone positioning increased with ARDS severity (52/128 (44%), 243/426 (57%) and 229/298 (77%), p < 0.001, in mild, moderate and severe ARDS, respectively). Prone positioning was first applied 2 [1–4] days after ICU admission, and a median of 3 [1–4] pronation sessions per patient was performed.

Table 1 outlines the principal differences between the two groups (additional information is summarized in Additional file 1, Table E2). No difference in comorbidities was observed (Charlson Comorbidity Index 2 [1–3] vs. 2 [1–3], p = 0.165). Patients in the PP group had significantly more severe respiratory disease, as suggested by a higher percentage of severe ARDS (44% vs. 21%, p < 0.001) and a lower percentage of mild ARDS (10 vs. 23%, p < 0.001). Respiratory rate, positive end-expiratory pressure (PEEP), FiO2 and Plateau pressure were significantly higher, while respiratory system compliance, PaO2/FiO2 ratio and arterial pH at ICU admission were significantly lower in the PP group. In addition, biochemical markers of inflammation and disease severity, such as LDH, D-dimers and ferritin, were consistently higher in patients of the PP Group. Patients of the PP group had higher severity scores: SOFA (4 [3–5] vs. 4 [3–4], p < 0.001) and APACHE II scores (10 [8–13] vs. 9 [7–13], p < 0.001). Finally, ICU mortality and length of stay, length of mechanical ventilation and hospital mortality and length of stay were all significantly worse in patients in the PP group.

Physiological Effects of Prone Position

In the subgroup of 78 patients, median duration of the first pronation was 18.5 [16–22] hours. Respiratory system compliance did not change significantly with the change in body position (Figure 1a). Similarly, on average, prone positioning had no significant effect on ventilatory ratio (Figure 1c). Overall, prone positioning led to a significant increase in PaO2/FiO2 ratio, which was followed by a subsequent significant decrease with re-supination (Figure 1b). On average, PaO2/FiO2 ratio after re-supination remained significantly higher as compared to baseline values. Table 2 summarizes the physiologic variables at the three different time points selected for the analysis.

Figure 1.

Physiological parameters' changes during the first session of prone positioning

O2-responders Versus O2-non-responders

Sixty-one out of 78 patients (78%) had an increase in PaO2/FiO2 ratio ≥ 20 mmHg (median increase 68 [42–117] mmHg) and where therefore defined as O2-Responders. Seventeen (22%) patients had an increase in PaO2/FiO2 ratio < 20 mmHg (median variation 3 [1–12] mmHg) and were therefore classified as O2-Non-Responders. Individual variations in PaO2/FiO2 ratio due to the change in body position in O2-Responders and O2 -Non-Responders are reported in Figure 2a, b, respectively. Table 3 summarizes the differences between O2 -Responders and O2-Non-Responders (for additional information see Additional file 1, Table E3). Demographics, comorbidities and admission severity scores were similar between O2-Responders and O2 -Non-Responders.

Figure 2.

Individual variations in PaO2/FiO2 ratio in Responders and Non-Responders during the first session of prone positioning

Notably, at ICU admission, driving pressure (14 [12–15] vs. 12 [8–13] cmH2O, p = 0.022), plateau pressure (27 [24–28] vs. 24 [22–27] cmH2O, p = 0.043) and respiratory system compliance (34 [30–45] vs. 45 [34–56] mL/cmH2O, p = 0.018) were significantly different between O2-Responders and O2 -Non-Responders. Moreover, prior to first pronation, baseline driving pressure (14 [11–16] vs. 11 [10–13] cmH2O, p = 0.036), respiratory rate (22 [20–24] vs. 20 [18–22] breaths per minute, p = 0.014), PaCO2 (58 [50–67] vs. 52 [45–60] mmHg, p = 0.092) and ventilatory ratio (2.2 [1.9–2.7] vs. 1.9 [1.6–2.2], p = 0.014) were higher in O2-Non-Responders, while Respiratory System Compliance (33 [26–45] vs. 44 [33–51] mL/cmH2O, p = 0.029), and pH (7.33 [7.31–7.38] vs. 7.37 [7.34–7.40], p = 0.041) were lower. When dividing the overall population in tertiles of pre-pronation driving pressure, a significantly different variation in PaO2/FiO2 ratio was observed, with patients with lower driving pressures having greater increase in PaO2/FiO2 ratio (Additional file 1: Figure E2). ICU mortality (11/17, 65% vs. 23/61, 38%, p = 0.047) was higher in O2-Non-Responders. Similar results were observed using a 10–20% increase in PaO2/FiO2 ratio as cut off (8/11, 72% vs. 26/67, 39%, p = 0.035 at 10% increase in PaO2/FiO2 ratio and 9/15, 60% vs. 25/63, 40%, p = 0.154 at 20% increase in PaO2/FiO2 ratio).

CO2-responders Versus CO2-non Responders

Thirty-seven out of 78 patients (47%) reduced their ventilatory ratio during prone position (median ΔVR − 0.21 [− 0.36 to − 0.10]) and where therefore defined as CO2-Responders. In 41 (53%) patients, the ventilatory ratio did not change or increased in prone position (median ΔVR 0.28 [0.09–0.54]): These patients were therefore defined as CO2-Non Responders. Differences between Responders and Non-Responders in terms of CO2 clearance are summarized in Additional file 1, Table E4. In summary, no differences were observed in the two populations, except for older age (65 [59–70] years vs. 56 [50–64] years, p = 0.005) and higher prevalence of hypertension (68% vs. 34%, p = 0.003) in CO2-Non Responders. ICU mortality did not differ between the two groups (19/37, 51% vs. 15/41, 37%, p = 0.189 in CO2-Responders and CO2-Non-Responders, respectively).