Comparative analysis of standard versus prolonged prone positioning in C-ARDS: outcomes on oxygenation and respiratory mechanics

Background: The COVID-19 pandemic has led to increased prevalence of COVID-19-associated Acute Respiratory Distress Syndrome (C-ARDS) in intensive care units (ICUs). Prone positioning (PP) is recommended for managing ARDS to improve oxygenation and respiratory mechanics. However, the optimal duration of PP and its impact on ventilator-free days (VFD) and ICU mortality remains unclear. Methods: This retrospective cohort study analyzed the data of 350 C-ARDS patients intubated within 24 hours of ICU admission in the period between March 2019 and January 2023. Patients were placed in two groups based on PP duration, i.e., standard PP (SPP, 16–24 hours) and prolonged PP (PPP, 25–36 hours). The primary outcome was the ICU mortality, and secondary outcomes were VFD, changes in respiratory mechanics and oxygenation indices in pre-prone, prone and post-prone periods. Results: SPP and PPP improved the oxygenation with significant increase in the Partial pressure of Oxygen/Fraction of inspired Oxygen (PaO2/FiO2) ratio and (PaO2/FiO2) ratio/Positive End-Expiratory Pressure (PF/PEEP) values in prone period compared to the pre-prone. Not much difference in ICU mortality or VFD was observed between the groups. Subgroup analyses showed that the survivors had lower driving pressure (DP) and mechanical power (MP) compared to those of the non-survivors. Conclusions: Both SPP and PPP improved the oxygenation, however no survival advantage was observed with prolonged prone sessions. PP is effective for lung-protective ventilation, and its duration should be adjusted based on the patient-specific factors. Further studies are required to optimize the PP durations for managing C-ARDS. Clinical Trial Registration: ClinicalTrials.gov, Registration ID: NCT06530095.

Acute respiratory distress syndrome; COVID-19; Lung recruitment; Prone position; Respiratory mechanics; Ventilator-induced lung injury

[1] Azagew AW, Beko ZW, Ferede YM, Mekonnen HS, Abate HK, Mekonnen CK. Global prevalence of COVID-19-induced acute respiratory distress syndrome: systematic review and meta-analysis. Systematic Reviews. 2023; 12: 212.

[2] Van der Ven FLIM, Blok SG, Azevedo LC, Bellani G, Botta M, Estenssoro E, et al.; ERICC–, LUNG SAFE–, PRoVENT–COVID–, EPICCoV–, CIBERESUCICOVID–, SATI–COVID–19–investigators. Epidemiology, ventilation management and outcomes of COVID-19 ARDS patients versus patients with ARDS due to pneumonia in the Pre-COVID era. Respiratory Research. 2024; 25: 312.

[3] ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012; 307: 2526–2533.

[4] Parada-Gereda HM, Avendaño JM, Melo JE, Ruiz CI, Castañeda MI, Medina-Parra J, et al. Association between ventilatory ratio and mortality in patients with acute respiratory distress syndrome and COVID 19: a multicenter, retrospective cohort study. BMC Pulmonary Medicine. 2023; 23: 425.

[5] Guervilly C, Fournier T, Chommeloux J, Arnaud L, Pinglis C, Baumstarck K, et al. Ultra-lung-protective ventilation and biotrauma in severe ARDS patients on veno-venous extracorporeal membrane oxygenation: a randomized controlled study. Critical Care. 2022; 26: 383.

[6] Pan C, Grieco DL, Zhou JX. Editorial: acute respiratory distress syndrome: lung protective strategy. Frontiers in Medicine. 2023; 9: 1121297.

[7] Boffi A, Ravenel M, Lupieri E, Schneider A, Liaudet L, Gonzalez M, et al. Physiological response to prone positioning in intubated adults with COVID-19 acute respiratory distress syndrome: a retrospective study. Respiratory Research. 2022; 23: 320.

[8] Protti A, Santini A, Pennati F, Chiurazzi C, Ferrari M, Iapichino GE, et al. Lung response to prone positioning in mechanically-ventilated patients with COVID-19. Critical Care. 2022; 26: 127.

[9] Carsetti A, Damia Paciarini A, Marini B, Pantanetti S, Adrario E, Donati A. Prolonged prone position ventilation for SARS-CoV-2 patients is feasible and effective. Critical Care. 2020; 24: 225.

[10] Petrone P, Brathwaite CEM, Joseph DK. Prone ventilation as treatment of acute respiratory distress syndrome related to COVID-19. European Journal of Trauma and Emergency Surgery. 2021; 47: 1017–1022.

[11] Rezoagli E, Chen L, Bellani G. Editorial: lung monitoring in respiratory failure. Frontiers in Medicine. 2023; 10: 1155898.

[12] Jochmans S, Mazerand S, Chelly J, Pourcine F, Sy O, Thieulot-Rolin N, et al. Duration of prone position sessions: a prospective cohort study. Annals of Intensive Care. 2020; 10: 66.

[13] Yehya N, Harhay MO, Curley MAQ, Schoenfeld DA, Reeder RW. Reappraisal of ventilator-free days in critical care research. American Journal of Respiratory and Critical Care Medicine. 2019; 200: 828–836.

[14] Phoophiboon V, Owattanapanich N, Owattanapanich W, Schellenberg M. Effects of prone positioning on ARDS outcomes of trauma and surgical patients: a systematic review and meta-analysis. BMC Pulmonary Medicine. 2023; 23: 504.

[15] Okin D, Huang CY, Alba GA, Jesudasen SJ, Dandawate NA, Gavralidis A, et al. Prolonged prone position ventilation is associated with reduced mortality in intubated COVID-19 patients. Chest. 2023; 163: 533–542.

[16] Rezoagli E, Mariani I, Rona R, Foti G, Bellani G. Difference between prolonged versus standard duration of prone position in COVID-19 patients: a retrospective study. Minerva Anestesiologica. 2021; 87: 1383–1385.

[17] Karlis G, Markantonaki D, Kakavas S, Bakali D, Katsagani G, Katsarou T, et al. Prone position ventilation in severe ARDS due to COVID-19: comparison between prolonged and intermittent strategies. Journal of Clinical Medicine. 2023; 12: 3526.

[18] Laghlam D, Charpentier J, Hamou ZA, Nguyen LS, Pene F, Cariou A, et al. Effects of prone positioning on respiratory mechanics and oxygenation in critically ill patients with COVID-19 requiring venovenous extracorporeal membrane oxygenation. Frontiers in Medicine. 2022; 8: 810393.

[19] Cornejo RA, Montoya J, Gajardo AIJ, Graf J, Alegría L, Baghetti R, et al.; SOCHIMI Prone-COVID-19 Group. Continuous prolonged prone positioning in COVID-19-related ARDS: a multicenter cohort study from Chile. Annals of Intensive Care. 2022; 12: 109.

[20] Hoppe K, Khan E, Meybohm P, Riese T. Mechanical power of ventilation and driving pressure: two undervalued parameters for pre extracorporeal membrane oxygenation ventilation and during daily management? Critical Care. 2023; 27: 111.

[21] Aoyama H, Pettenuzzo T, Aoyama K, Pinto R, Englesakis M, Fan E. Association of driving pressure with mortality among ventilated patients with acute respiratory distress syndrome: a systematic review and meta-analysis. Critical Care Medicine. 2018; 46: 300–306.

[22] Goligher EC, Costa ELV, Yarnell CJ, Brochard LJ, Stewart TE, Tomlinson G, et al. Effect of lowering Vt on mortality in acute respiratory distress syndrome varies with respiratory system elastance. American Journal of Respiratory and Critical Care Medicine. 2021; 203: 1378–1385.

[23] Writing Group for the PReVENT Investigators; Simonis FD, Serpa Neto A, Binnekade JM, Braber A, Bruin KCM, Determann RM, et al. Effect of a low vs. intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: a randomized clinical trial. JAMA. 2018; 320: 1872–1880.

[24] Pereira Romano ML, Maia IS, Laranjeira LN, Damiani LP, Paisani DM, Borges MC, et al. Driving pressure-limited strategy for patients with acute respiratory distress syndrome. A pilot randomized clinical trial. Annals of the American Thoracic Society. 2020; 17: 596–604.

[25] Costa ELV, Slutsky AS, Brochard LJ, Brower R, Serpa-Neto A, Cavalcanti AB, et al. Ventilatory variables and mechanical power in patients with acute respiratory distress syndrome. American Journal of Respiratory and Critical Care Medicine. 2021; 204: 303–311.

[26] Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, et al.; Expiratory Pressure (Express) Study Group. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008; 299: 646–655.

[27] Beitler JR, Guérin C, Ayzac L, Mancebo J, Bates DM, Malhotra A, et al. PEEP titration during prone positioning for acute respiratory distress syndrome. Critical Care. 2015; 19: 436.

[28] Schmidt M, Hajage D, Lebreton G, Dres M, Guervilly C, Richard JC, et al. PRONECMO investigators, the REVA network, and the international ECMO network (ECMONet). Prone positioning during extracorporeal membrane oxygenation in patients with severe ARDS: the PRONECMO randomized clinical trial. JAMA. 2023; 330: 2343–2353.

[29] Walter T, Zucman N, Mullaert J, Thiry I, Gernez C, Roux D, et al. Extended prone positioning duration for COVID-19-related ARDS: benefits and detriments. Critical Care. 2022; 26: 208.