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


Study Design

This Italian multicentre, retrospective study of prospectively collected data was approved by the Ethical Committees of all participating centres (Promoting Centre's Ethical Committee: Comitato Etico Milano Area 2; protocol: 0008489; date of approval: March 20, 2020) and registered at (NCT04388670). The need for informed consent from individual patients was waived owing to the retrospective nature of the study.

All patients admitted between February 22, 2020, and June 14, 2020, inclusive for those days, to the COVID-19 ICUs of 24 Italian hospitals (see Additional file 1: Table E1 for the complete list) were screened for eligibility. Laboratory-confirmed SARS-CoV-2 infection, (i.e. positive result of real-time reverse transcriptase–polymerase chain reaction assay of nasal and pharyngeal swabs), and ICU admission for ARDS, defined by the Berlin criteria,[19] constituted the inclusion criteria. Exclusion criteria were age < 18 years, patients treated exclusively with non-invasive respiratory support and missing clinical data regarding the use of prone position. Clinical management (including mechanical ventilation setting and pharmacological therapies) followed the local treatment guidelines of each centre. The choice to position patients prone was at discretion of the attending physician.

The population of patients included in the analysis was subdivided in two groups according to the use of prone positioning: (1) PP group: patients who were turned prone at least once during their ICU stay; and (2) SP group: patients always treated in the supine position.

Data Collection

An electronic case report form (REDCap electronic data capture tools) hosted at IRCCS Ca' Granda Ospedale Maggiore Policlinico was used for data collection. An extensive set of information regarding demographic and anthropometric data, comorbidities[20] and clinical data (severity scores,[21–23] vital signs, type of respiratory support, use of prone positioning, respiratory parameters, laboratory tests including blood gas analysis) was collected on the day of admission to the ICU. Relevant clinical and laboratory data, including information regarding the use of prone positioning in the prior 24 h, were then collected daily until ICU discharge or patient death.

Finally, the following patient outcomes were recorded: ICU and hospital survival, ICU and hospital length of stay (LOS), duration of invasive mechanical ventilation. The final date of follow-up for patient outcomes were July 15, 2020.

Effect of Prone Positioning on Respiratory Mechanics and Gas Exchange

To assess the physiologic effects of pronation, a subgroup of 78 patients who underwent prone positioning in two of the participating hospitals (Grande Ospedale Metropolitano Niguarda and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, both in Milan) was investigated at three different time points: (1) prior to the first pronation (Baseline); (2) during the last hour of the first session of prone ventilation (Prone); and (3) within 4 h after turning the patients back to supine position (Supine). At each time-point, end-inspiratory and end-expiratory airway occlusion manoeuvres were performed and arterial blood gases analyzed to obtain the following variables: compliance of the respiratory system (Crs, calculated as the ratio between tidal volume and airway driving pressure); ratio between partial pressure of oxygen (PaO2) and inspired fraction of oxygen (FiO2),—PaO2/FiO2 ratio; corrected minute ventilation[24] and ventilatory ratio.[25] Patients were defined as "O2-Responders", if they had an increase in the PaO2/FiO2 ratio of ≥ 20 mmHg during prone ventilation as compared to baseline values in supine position.[26,27] Moreover, patients were defined as Responders in terms of carbon dioxide (CO2) clearance, "CO2 -Responders", if their ventilatory ratio was reduced during prone ventilation, as compared to baseline values in supine position, i.e. if the difference between ventilatory ratio in prone position and ventilatory ratio at baseline (ΔVR) was < 0.

Statistical Analysis

Continuous variables are presented as mean with standard deviation (SD) or median and interquartile range (IQR). Categorical variables are expressed as frequencies (percentages).

Mann–Whitney rank sum test was used to compare nonparametric continuous variables between study groups. χ 2 or Fisher exact test was used for categorical variables, as appropriate.

Differences among time-points were tested by one-way ANOVA for repeated measures or Friedman Repeated Measures Analysis of Variance on Ranks, as appropriate. Pairwise multiple comparisons were tested using Tukey's test. Differences among tertiles of pre-pronation driving pressure were tested by one-way ANOVA on ranks. Pairwise multiple comparisons were tested using Dunn's Method. All statistical tests were 2-tailed, and statistical significance was defined as a p value below 0.05. Analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA), STATA computer software, version 16.0 (StataCorp LLC) and SigmaPlot 12.0 (Systat Software Inc., San Jose, CA).