Effect of Awake Prone Positioning in non-Intubated COVID-19 Patients with Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-Analysis
Abstract
Background
Awake prone positioning (APP) has been considered as a feasible treatment for patients with acute hypoxemic respiratory failure in non-intubated coronavirus disease 2019 (COVID-19). However, the efficacy and safety of APP remain uncertain. This meta-analysis aims to assess the effect of APP on intubation rate and mortality in COVID-19 patients with acute respiratory failure.
Methods
Relevant studies published from January 1, 2020, to June 17, 2022, were systematically searched. The primary outcomes were the intubation rate and mortality; the secondary outcome was the incidence of adverse events.
Results
Of 5746 identified publications, 22 were eligible for inclusion in the meta-analysis (N = 5146 patients). In comparison to the non-APP group, APP could decrease the intubation rates (OR 0.64; 95% CI 0.48-0.83; P = .001), particularly in the subgroup of the daily median duration of APP > 8 h and in the subgroup of receiving high flow nasal cannula (HFNC) or non-invasive ventilation (NIV). Patients treated with APP were associated with lower mortality rates (OR 0.61; 95% CI 0.45-0.81; P = .0008), but no mortality benefit was found in the APP group in the subgroup of randomized controlled trials (RCTs). No significant difference was found in the incidence of adverse events between the groups (OR 1.13; 95% CI 0.75-1.71; P = .56).
Conclusion
Our results demonstrated that APP could be an effective strategy to avoid intubation without detrimental effects in non-intubated patients with COVID-19, especially for patients requiring HFNC or NIV, and the daily APP duration with the target of minimally eight hours was suggested. In the subgroup of RCTs, the pooled results did not demonstrate any benefit of APP on mortality. Given the limited number of RCTs, further high-quality RCTs are needed to confirm the results.
INPLASY registration number
INPLASY2021110037.
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Data availability statement
All data analyzed during this meta-analysis are included in this published article and its supplementary information files.
References
1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. Jama. 2020;323(13):1239–1242.
2. WHO. COVID-19 Clinical management: living guidance. 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1.
3. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. Jama. 2020;323(16):1574–1581.
4. Xie J, Wu W, Li S, et al. Clinical characteristics and outcomes of critically ill patients with novel coronavirus infectious disease (COVID-19) in China: a retrospective multicenter study. Intensive Care Med. 2020;46(10):1863–1872.
5. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York city: a prospective cohort study. Lancet. 2020;395(10239):1763–1770.
6. Hua J, Qian C, Luo Z, Li Q, Wang F. Invasive mechanical ventilation in COVID-19 patient management: the experience with 469 patients in Wuhan. Crit Care. 2020;24(1):348.
7. Wang Y, Lu X, Li Y, et al. Clinical course and outcomes of 344 intensive care patients with COVID-19. Am J Respir Crit Care Med. 2020;201(11):1430–1434.
8. Subgroup of Critical Respiratory Diseases. Standardized protocol of prone position ventilation in patients with acute respiratory distress syndrome. Zhonghua Nei Ke Za Zhi 2020;59(10):781–787.
9. Scholten EL, Beitler JR, Prisk GK, Malhotra A. Treatment of ARDS with prone positioning. Chest. 2017;151(1):215–224.
10. Guérin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020;46(12):2385–2396.
11. Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159–2168.
12. Bloomfield R, Noble DW, Sudlow A. Prone position for acute respiratory failure in adults. Cochrane Database Syst Rev. 2015;2015(11):Cd008095.
13. Munshi L, Del Sorbo L, Adhikari NKJ, et al. Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc. 2017;14(Supplement_4):S280–S288.
14. Scaravilli V, Grasselli G, Castagna L, et al. Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: a retrospective study. J Crit Care. 2015;30(6):1390–1394.
15. Ding L, Wang L, Ma W, He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Crit Care. 2020;24(1):28.
16. Coppo A, Bellani G, Winterton D, et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study. Lancet Respir Med. 2020;8(8):765–774.
17. Sartini C, Tresoldi M, Scarpellini P,. et al. Respiratory parameters in patients with COVID-19 after using noninvasive ventilation in the prone position outside the intensive care unit. Jama. 2020;323(22):2338–2340.
18. Pavlov I, He H, McNicholas B, et al. Awake Prone Positioning in Non-Intubated Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19. Respir Care. 2022;67(1):102–114.
19. Chua EX, Zahir SMISM, Ng KT,. et al. Effect of prone versus supine position in COVID-19 patients: a systematic review and meta-analysis. J Clin Anesth. 2021;74:110406.
20. Beran A, Mhanna M, Srour O, et al. Effect of prone positioning on clinical outcomes of non-intubated subjects with COVID-19: a comparative systematic review and meta-analysis. Respir Care. 2022;67(4):471–479.
21. Ehrmann S, Li J, Ibarra-Estrada M, et al. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med. 2021;9(12):1387–1395.
22. Alhazzani W, Parhar KKS, Weatherald J, et al. Effect of awake prone positioning on endotracheal intubation in patients with COVID-19 and acute respiratory failure: a randomized clinical trial. Jama. 2022;327(21):2104–2113.
23. Qian ET, Gatto CL, Amusina O, et al. Assessment of awake prone positioning in hospitalized adults with COVID-19: a nonrandomized controlled trial. JAMA Intern Med. 2022;182(6):612–621.
24. Ibarra-Estrada M, Li J, Pavlov I, et al. Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial. Crit Care. 2022;26(1):84.
25. Fralick M, Colacci M, Munshi L, et al. Prone positioning of patients with moderate hypoxaemia due to COVID-19: multicentre pragmatic randomised trial (COVID-PRONE). Br Med J. 2022;376:e068585.
26. Alhazzani W, Evans L, Alshamsi F, et al. Surviving sepsis campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021;49(3):e219–e234.
27. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Br Med J. 2011;343:d5928.
28. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–605.
29. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Br Med J. 2003;327(7414):557–560.
30. Rosén J, von Oelreich E, Fors D, et al. Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial. Crit Care. 2021;25(1):209.
31. Jayakumar D, Ramachandran DP, Rabindrarajan DE, Vijayaraghavan MBKT, Ramakrishnan AN, Venkataraman AR. Standard care versus awake prone position in adult nonintubated patients with acute hypoxemic respiratory failure secondary to COVID-19 infection—a multicenter feasibility randomized controlled trial. J Intensive Care Med. 2021;36(8):918–924.
32. Johnson SA, Horton DJ, Fuller MJ,. et al. Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization (PAPR). Ann Am Thorac Soc. 2021;18(8):1424–1426.
33. Prud’homme E, Trigui Y, Elharrar X, et al. Effect of prone positioning on the respiratory support of nonintubated patients with COVID-19 and acute hypoxemic respiratory failure: a retrospective matching cohort study. Chest. 2021;160(1):85–88.
34. Zang X, Wang Q, Zhou H, et al. Efficacy of early prone position for COVID-19 patients with severe hypoxia: a single-center prospective cohort study. Intensive Care Med. 2020;46(10):1927–1929.
35. Tonelli R, Pisani L, Tabbì L, et al. Early awake proning in critical and severe COVID-19 patients undergoing noninvasive respiratory support: a retrospective multicenter cohort study. Pulmonology. 2022;28(3):181–192.
36. Sryma PB, Mittal S, Mohan A, et al. Effect of proning in patients with COVID-19 acute hypoxemic respiratory failure receiving noninvasive oxygen therapy. Lung India. 2021;38(Supplement):S6–S10.
37. Esperatti M, Busico M, Fuentes NA, et al. Impact of exposure time in awake prone positioning on clinical outcomes of patients with COVID-19-related acute respiratory failure treated with high-flow nasal oxygen: a multicenter cohort study. Crit Care. 2022;26(1):16.
38. Perez-Nieto OR, Escarraman-Martinez D, Guerrero-Gutierrez MA, et al. Awake prone positioning and oxygen therapy in patients with COVID-19: the APRONOX study. Eur Respir J. 2022;59(2):2100265.
39. Jouffroy R, Darmon M, Isnard F, et al. Impact of prone position in non-intubated spontaneously breathing patients admitted to the ICU for severe acute respiratory failure due to COVID-19. J Crit Care. 2021;64:199–204.
40. Barker J, Pan D, Koeckerling D, Baldwin AJ, West R. Effect of serial awake prone positioning on oxygenation in patients admitted to intensive care with COVID-19. Postgrad Med J. 2022;98(1159):360–364.
41. Altinay M, Sayan I, Turk HS, et al. Effect of early awake prone positioning application on prognosis in patients with acute respiratory failure due to COVID-19 pneumonia: a retrospective observational study. Braz J Anesthesiol. 2022;72(2):194–199.
42. Taylor SP, Bundy H, Smith WM, Skavroneck S, Taylor B, Kowalkowski MA. Awake-prone positioning strategy for non-intubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation. Ann Am Thorac Soc. 2021;18(8):1360–1368.
43. Padrão EMH, Valente FS, Besen BAMP, et al. Awake prone positioning in COVID-19 hypoxemic respiratory failure: exploratory findings in a single-center retrospective cohort study. Acad Emerg Med. 2020;27(12):1249–1259.
44. Ni Z, Wang K, Wang T, et al. Efficacy of early prone or lateral positioning in patients with severe COVID-19: a single-center prospective cohort. Precis Clin Med. 2020;3(4):260–271.
45. Jagan N, Morrow LE, Walters RW,. et al. The POSITIONED study: prone positioning in nonventilated coronavirus disease 2019 patients-a retrospective analysis. Crit Care Explor. 2020;2(10):e0229.
46. Ferrando C, Mellado-Artigas R, Gea A, et al. Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study. Crit Care. 2020;24(1):597.
47. Sarma A, Calfee CS. Prone positioning in awake, nonintubated patients with COVID-19: necessity is the mother of invention. JAMA Intern Med. 2020;180(11):1539–1540.
48. Touchon F, Trigui Y, Prud’homme E, et al. Awake prone positioning for hypoxaemic respiratory failure: past, COVID-19 and perspectives. Eur Respir Rev. 2021;30(160):210022.
49. Gattinoni L, Taccone P, Carlesso E, Marini JJ. Prone position in acute respiratory distress syndrome. Rationale, indications, and limits. Am J Respir Crit Care Med. 2013;188(11):1286–1293.
50. Kangelaris KN, Ware LB, Wang CY,. et al. Timing of intubation and clinical outcomes in adults with acute respiratory distress syndrome. Crit Care Med. 2016;44(1):120–129.
51. Li J, Luo J, Pavlov I, et al. Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis. Lancet Respir Med. 2022;10(6):573–583.
52. Behesht Aeen F, Pakzad R, Goudarzi Rad M, Abdi F, Zaheri F, Mirzadeh N. Effect of prone position on respiratory parameters, intubation and death rate in COVID-19 patients: systematic review and meta-analysis. Sci Rep. 2021;11(1):14407.
53. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934–943.
54. Kao KC, Chang KW, Chan MC, et al. Predictors of survival in patients with influenza pneumonia-related severe acute respiratory distress syndrome treated with prone positioning. Ann Intensive Care. 2018;8(1):94.
55. Gattinoni L, Vagginelli F, Carlesso E, et al. Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome. Crit Care Med. 2003;31(12):2727–2733.
56. Dardeir A, Marudhai S, Patel M, Ghani MR, Busa V. Factors influencing prone positioning in treating acute respiratory distress syndrome and the effect on mortality rate. Cureus. 2020;12(10):e10767.
57. Kaur R, Vines DL, Mirza S, et al. Early versus late awake prone positioning in non-intubated patients with COVID-19. Crit Care. 2021;25(1):340.
58. Mancebo J, Fernández R, Blanch L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;173(11):1233–1239.
59. Taccone P, Pesenti A, Latini R, et al. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. Jama. 2009;302(18):1977–1984.
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Article first published online: August 25, 2022
Issue published: November 2022
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PubMed: 36017576
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ZT came up with the idea, HK and XG contributed to the literature search, data collection, study design, and data analysis. HK drafted the manuscript. ZT revised the final manuscript.
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