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Prone ventilation in intubated COVID-19 patients: a systematic review and meta-analysis

Ee Xin Chua Zhen Zhe Wong Mohd Shahnaz Hasan Rafidah Atan Nor'azim Mohd Yunos Hing Wa Yip Wan Yi Teoh Mohd Afiq Syahmi Ramli Ka Ting Ng About the authors

Abstract

Background

The efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients.

Methods

Databases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded.

Results

Eleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p= 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p= 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p= 0.28; evidence: very low).

Conclusion

Prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

KEYWORDS
Acute respiratory distress syndrome; COVID-19; Intubation; Prone position; Supine position; Ventilation

Introduction

Severe pneumonia secondary to Coronavirus Disease 2019 (COVID-19) is associated with reduced peripheral oxygen saturation (SpO2) of < 94%, low ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) of < 300 mmHg, marked tachypnea (respiratory rate of > 30 breaths per minute), and lung infiltrates of > 50%.11 Attaway AH, Scheraga RG, Bhimraj A, et al. Severe covid-19 pneumonia: pathogenesis and clinical management. BMJ. 2021;372:n436. Studies have reported that 15-30% of patients hospitalized for COVID-19 will develop severe pneumonia and hypoxemia,11 Attaway AH, Scheraga RG, Bhimraj A, et al. Severe covid-19 pneumonia: pathogenesis and clinical management. BMJ. 2021;372:n436. many of which will require treatment in the intensive care unit.22 Meng L, Qiu H, Wan L, et al. Intubation and ventilation amid the COVID-19 outbreak: Wuhan's experience. Anesthesiology. 2020;132:1317-32. In severe COVID-19 pneumonia, patients may progress to develop Acute Respiratory Distress Syndrome (ARDS),22 Meng L, Qiu H, Wan L, et al. Intubation and ventilation amid the COVID-19 outbreak: Wuhan's experience. Anesthesiology. 2020;132:1317-32. and up to 88% of patients with COVID-19 in the intensive care unit require endotracheal intubation to maintain oxygenation.33 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;323:1574-81. Several observational studies reported that severe mechanically ventilated COVID-19 pneumonia patients were associated with high mortality of 27-31% in the intensive care unit.33 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;323:1574-81.,44 Auld SC, Caridi-Scheible M, Blum JM, et al. ICU and ventilator mortality among critically Ill adults with coronavirus disease 2019. Crit Care Med. 2020;48:e799-804.

The application of the prone position during mechanical ventilation has been previously studied to improve oxygenation and reduce mortality in classical ARDS prior to the emergence of COVID-19.55 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:S280-8.,66 Mora-Arteaga JA, Bernal-Ramírez OJ, Rodríguez SJ. The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis. Med Intensiva (Engl Ed). 2015;39:359-72. At present, the World Health Organization (WHO) recommends the use of the prone position in patients with severe COVID-19 who require noninvasive ventilation based on the evidence of its benefit seen in classical ARDS.77 WHO. COVID-19 Clinical management: living guidance. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 . [Accessed 1 May 2021]
https://www.who.int/publications/i/item/...
A recent meta-analysis demonstrated that prone positioning improved oxygenation parameters (PaO2/FiO2 ratio and SpO2) in awake spontaneously breathing COVID-19 patients.88 Cardona S, Downing J, Alfalasi R, et al. Intubation rate of patients with hypoxia due to COVID-19 treated with awake proning: a meta-analysis. Am J Emerg Med. 2021;43:88-96. However, the safety and efficacy profiles of prone ventilation in patients with severe COVID-19 requiring intubation remain unclear in the literature. Thus, a systematic review and meta-analysis is timely warranted to synthesize evidence on the use of prone ventilation in intubated COVID-19 patients before any recommendation can be made with certainty.

We hypothesized that prone ventilation improved oxygenation in intubated COVID-19 patients. The primary objective of this review was to examine the effect of prone ventilation on the PaO2/FiO2 ratio in intubated COVID-19 patients. Secondary objectives were to investigate the effects of prone ventilation on SpO2, arterial partial pressure of carbon dioxide (PaCO2), mortality rate, and number of patients discharged alive in intubated COVID-19 patients.

Methods

This review was conducted and reported according to the Cochrane Handbook for Systematic Reviews and Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), respectively.99 Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. Wiley-Blackwell; 2019.,1010 Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. The protocol of this review was published on PROSPERO (CRD42021241364) before the commencement of the literature search. Review questions were formulated using the Population, Intervention, Control, and Outcomes (PICO) approach, as shown in Supplemental Table E1. The primary outcome was the PaO2/FiO2 ratio after prone and supine ventilation. Secondary outcomes included SpO2, PaCO2, mortality rate, and number of patients discharged alive.

Databases of Ovid MEDLINE, Ovid EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched systematically from their inception until March 2021. The list of search items and strategy is presented in Supplemental Table E2. The inclusion criteria were any randomized-controlled trials or observational studies (retrospective or prospective) comparing prone and supine ventilation in adult (ages ≥ 18 years) intubated COVID-19 patients. The bibliography of the included studies was searched for any additional articles. Trial registries (clinicaltrials.gov and WHO International Clinical Trials Registry Platform Search Portal) were also searched for any ongoing studies. All case reports, case series, and editorials were excluded in this review.

The title-abstracts and full texts were screened according to the predefined inclusion and exclusion criteria by two authors (EC and ZW) independently. Any disagreement during the screening and selection of studies were resolved by consulting a third author (KN). The final list of included studies was agreed on by all the authors. Two authors (EC and ZW) extracted data independently using an online data extraction sheet. A third author (KN) cross-checked all the extracted data for any discrepancies. Any data that was presented in the form of median and interquartile range was converted to mean and standard deviation for data pooling.1111 Wan X, Wang W, Liu J, et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. The corresponding authors of the included studies were contacted at least twice if there was any unclear or missing data. In addition to the measured outcomes, other relevant data, namely authors, year of publication, sample size, age, duration of prone ventilation, enrollment criteria, and ventilation strategy were also extracted.

Two authors (EC and ZW) performed the risk of bias assessment for all the included studies independently, using the Newcastle-Ottawa Scale for non-randomized studies. It consists of three domains, namely selection, comparability, and outcome. Each domain was assessed using a star system with a maximum of 9 stars.1212 Wells GA, Shea B, O'Connor D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses. Available from: http://www.ohri.ca/programs/clinica-l_epidemiology/oxford.asp. [Accessed 1 May 2021]
http://www.ohri.ca/programs/clinica-l_ep...
Studies with a total score of 7 or more were considered as low risk of bias. The certainty of evidence was assessed based on the risk of bias, inconsistency, imprecision, indirectness, and publication bias. A third author (KN) was consulted for any disagreement in the assessment of risk of bias and certainty of evidence for all the included studies.

The Review Manager software (version 5.4) was used for statistical meta-analysis. Dichotomous and continuous parameters were reported using Odds Ratio (OR) and Mean Difference (MD), respectively, with a Confidence Interval (CI) of 95%. Any p-value of < 0.05 was considered statistically significant. The I-square (I2) test was used for assessment of statistical heterogeneity, with I2 of < 40% categorized as low heterogeneity, I2 of 40-60% as moderate heterogeneity, and I2 of > 60% as substantial heterogeneity. In view of limited studies of small sample size with significant heterogeneity, a random-effect model was used for all the measured outcomes.

Results

Our search generated a total of 1722 articles and 41 articles were eligible for full text screening (Fig. 1). Twenty-eight studies were excluded after applying the inclusion and exclusion criteria, as listed in Supplemental Table E3. A total of 14 studies (a total of 658 patients) were included in this review. However, only eleven studies (a total of 606 patients) were included in quantitative meta-analysis, as three of the included studies did not report any of the outcomes of interest.1313 Khullar R, Shah S, Singh G, et al. Effects of prone ventilation on oxygenation, inflammation, and lung infiltrates in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study. J Clin Med. 2020;9(12):4129.

14 Mittermaier M, Pickerodt P, Kurth F, et al. Evaluation of PEEP and prone positioning in early COVID-19 ARDS. EClinicalMedicine. 2020;28:100579.
-1515 Sang L, Zheng X, Zhao Z, et al. Lung recruitment, individualized PEEP, and prone position ventilation for COVID-19-associated severe ARDS: a single center observational study. Front Med (Lausanne). 2021;7:603943. Search on trial registries did not identify any ongoing studies comparing prone and supine ventilation in intubated COVID-19 patients.

Figure 1
PRISMA flow diagram.

The clinical characteristics of our included studies are listed in Table 1. All 14 studies were single center cohort studies (6 prospective,1414 Mittermaier M, Pickerodt P, Kurth F, et al. Evaluation of PEEP and prone positioning in early COVID-19 ARDS. EClinicalMedicine. 2020;28:100579.,1616 Astua AJ, Michaels EK, Michaels AJ. Proning During Pandemic: the rapid institution of a safe, transferable, and effective prone positioning program at Nychhc/elmhurst Hospital, a situationally resource limited facility, during the peak of the Covid 19 surge. Res Sq. 2020.

17 Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20.

18 Doussot A, Ciceron F, Cerutti E, et al. Prone positioning for severe acute respiratory distress syndrome in COVID-19 patients by a dedicated team: a safe and pragmatic reallocation of medical and surgical work force in response to the outbreak. Ann Surg. 2020;272:e311-5.

19 Abou-Arab O, Haye G, Beyls C, et al. Hypoxemia and prone position in mechanically ventilated COVID-19 patients: a prospective cohort study. Can J Anaesth. 2020;68:262-3.
-2020 Perier F, Tuffet S, Maraffi T, et al. Effect of positive end-expiratory pressure and proning on ventilation and perfusion in COVID-19 acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;202:1713-7. 8 retrospective1313 Khullar R, Shah S, Singh G, et al. Effects of prone ventilation on oxygenation, inflammation, and lung infiltrates in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study. J Clin Med. 2020;9(12):4129.,1515 Sang L, Zheng X, Zhao Z, et al. Lung recruitment, individualized PEEP, and prone position ventilation for COVID-19-associated severe ARDS: a single center observational study. Front Med (Lausanne). 2021;7:603943.,2121 Berrill M. Evaluation of oxygenation in 129 proning sessions in 34 mechanically ventilated COVID-19 Patients. J Intensive Care Med. 2020;36:229-32.

22 Douglas IS, Rosenthal CA, Swanson DD, et al. Safety and outcomes of prolonged usual care prone position mechanical ventilation to treat acute coronavirus disease 2019 hypoxemic respiratory failure. Crit Care Med. 2021;49:490-502.

23 Gleissman H, Forsgren A, Andersson E, et al. Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019. Acta Anaesthesiol Scand. 2021;65:360-3.

24 Sharp T, Al-Faham Z, Brown M, et al. Prone position in covid-19: can we tackle rising dead space?J Intensive Care Soc. 2020;0:1-4.

25 Shelhamer M, Wesson PD, Solari IL, et al. Prone positioning in moderate to severe acute respiratory distress syndrome due to COVID-19: a cohort study and analysis of physiology. J Intensive Care Med. 2021;36:241-52.
-2626 Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55.) Of all, only one study compared two separate cohorts of supine and prone ventilation in intubated COVID-19 patients.2525 Shelhamer M, Wesson PD, Solari IL, et al. Prone positioning in moderate to severe acute respiratory distress syndrome due to COVID-19: a cohort study and analysis of physiology. J Intensive Care Med. 2021;36:241-52. The rest were crossover cohort studies, in which patients underwent both supine and prone ventilation regimens. The sample size varied from 9 to 261 patients in the included studies. The mean age and Body Mass Index (BMI) of patients ranged from 52.8 to 69.5 years and from 27.9 to 36.5 kg.m−2, respectively. In terms of the settings of mechanical ventilation, the tidal volume varied across the included studies, ranging from 4 to 8 mL.kg−1 predicted body weight. The extrinsic Positive End-Expiratory Pressure (PEEP) used during mechanical ventilation also differed across the included studies. Most of our included studies used prolonged duration of prone ventilation per session, with the mean duration of prone ventilation ranging from 14.3 to 24 hours per session. The mean number of days of prone positioning ranged from 3.2 to 4.7 days across all the included studies.

Table 1
Clinical characteristics of included studies.

The risk of bias assessment for all the included studies and PRISMA checklist are summarized in Supplemental Tables E4 and E5. Out of all included studies, eleven studies were considered as low risk of bias as they scored at least 7 out of 9 stars based on the domains of selection, comparability, and outcome in the Newcastle-Ottawa Scale.1313 Khullar R, Shah S, Singh G, et al. Effects of prone ventilation on oxygenation, inflammation, and lung infiltrates in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study. J Clin Med. 2020;9(12):4129.

14 Mittermaier M, Pickerodt P, Kurth F, et al. Evaluation of PEEP and prone positioning in early COVID-19 ARDS. EClinicalMedicine. 2020;28:100579.
-1515 Sang L, Zheng X, Zhao Z, et al. Lung recruitment, individualized PEEP, and prone position ventilation for COVID-19-associated severe ARDS: a single center observational study. Front Med (Lausanne). 2021;7:603943.,1717 Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20.

18 Doussot A, Ciceron F, Cerutti E, et al. Prone positioning for severe acute respiratory distress syndrome in COVID-19 patients by a dedicated team: a safe and pragmatic reallocation of medical and surgical work force in response to the outbreak. Ann Surg. 2020;272:e311-5.
-1919 Abou-Arab O, Haye G, Beyls C, et al. Hypoxemia and prone position in mechanically ventilated COVID-19 patients: a prospective cohort study. Can J Anaesth. 2020;68:262-3.,2121 Berrill M. Evaluation of oxygenation in 129 proning sessions in 34 mechanically ventilated COVID-19 Patients. J Intensive Care Med. 2020;36:229-32.

22 Douglas IS, Rosenthal CA, Swanson DD, et al. Safety and outcomes of prolonged usual care prone position mechanical ventilation to treat acute coronavirus disease 2019 hypoxemic respiratory failure. Crit Care Med. 2021;49:490-502.
-2323 Gleissman H, Forsgren A, Andersson E, et al. Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019. Acta Anaesthesiol Scand. 2021;65:360-3.,2525 Shelhamer M, Wesson PD, Solari IL, et al. Prone positioning in moderate to severe acute respiratory distress syndrome due to COVID-19: a cohort study and analysis of physiology. J Intensive Care Med. 2021;36:241-52.,2626 Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55. Three studies were of high risk of bias as they had a total score < 7 due to potential bias in the comparability domain.1616 Astua AJ, Michaels EK, Michaels AJ. Proning During Pandemic: the rapid institution of a safe, transferable, and effective prone positioning program at Nychhc/elmhurst Hospital, a situationally resource limited facility, during the peak of the Covid 19 surge. Res Sq. 2020.,2020 Perier F, Tuffet S, Maraffi T, et al. Effect of positive end-expiratory pressure and proning on ventilation and perfusion in COVID-19 acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;202:1713-7.,2424 Sharp T, Al-Faham Z, Brown M, et al. Prone position in covid-19: can we tackle rising dead space?J Intensive Care Soc. 2020;0:1-4. The summary of findings for all measured outcomes and certainty of evidence are outlined in Table 2 and Table 3.

Table 2
Summary of findings for primary and secondary outcomes.
Table 3
GRADE assessment of primary and secondary outcomes.

Eight studies (n = 579 patients) examined the PaO2/FiO2 ratio after supine and prone ventilation.1616 Astua AJ, Michaels EK, Michaels AJ. Proning During Pandemic: the rapid institution of a safe, transferable, and effective prone positioning program at Nychhc/elmhurst Hospital, a situationally resource limited facility, during the peak of the Covid 19 surge. Res Sq. 2020.,1717 Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20.,1919 Abou-Arab O, Haye G, Beyls C, et al. Hypoxemia and prone position in mechanically ventilated COVID-19 patients: a prospective cohort study. Can J Anaesth. 2020;68:262-3.,2121 Berrill M. Evaluation of oxygenation in 129 proning sessions in 34 mechanically ventilated COVID-19 Patients. J Intensive Care Med. 2020;36:229-32.

22 Douglas IS, Rosenthal CA, Swanson DD, et al. Safety and outcomes of prolonged usual care prone position mechanical ventilation to treat acute coronavirus disease 2019 hypoxemic respiratory failure. Crit Care Med. 2021;49:490-502.

23 Gleissman H, Forsgren A, Andersson E, et al. Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019. Acta Anaesthesiol Scand. 2021;65:360-3.
-2424 Sharp T, Al-Faham Z, Brown M, et al. Prone position in covid-19: can we tackle rising dead space?J Intensive Care Soc. 2020;0:1-4.,2626 Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55. Intubated COVID-19 patients who received prone ventilation had significantly higher mean PaO2/FiO2 ratio compared to the supine ventilation group (MD = 46.75, 95% CI 33.35 to 60.15, p < 0.00001; Fig. 2). However, the observed statistical heterogeneity was substantial (I2= 78%). The certainty of evidence was graded as very low due to the observational studies in nature, inconsistency, and publication bias.

Figure 2
Forest plot of ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio).

Pooling of data from three studies (n = 432 patients) demonstrated that those with prone ventilation were associated with higher SpO2 (MD = 1.67, 95% CI 1.08 to 2.26, p < 0.00001; I2= 0%; certainty of evidence: low, Suppementary Fig. E1).1818 Doussot A, Ciceron F, Cerutti E, et al. Prone positioning for severe acute respiratory distress syndrome in COVID-19 patients by a dedicated team: a safe and pragmatic reallocation of medical and surgical work force in response to the outbreak. Ann Surg. 2020;272:e311-5.,2020 Perier F, Tuffet S, Maraffi T, et al. Effect of positive end-expiratory pressure and proning on ventilation and perfusion in COVID-19 acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;202:1713-7.,2626 Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55. Among all included studies, five of them (n = 396 patients) recorded the PaCO2 after mechanical ventilation in the prone and supine position.1616 Astua AJ, Michaels EK, Michaels AJ. Proning During Pandemic: the rapid institution of a safe, transferable, and effective prone positioning program at Nychhc/elmhurst Hospital, a situationally resource limited facility, during the peak of the Covid 19 surge. Res Sq. 2020.,1717 Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20.,2222 Douglas IS, Rosenthal CA, Swanson DD, et al. Safety and outcomes of prolonged usual care prone position mechanical ventilation to treat acute coronavirus disease 2019 hypoxemic respiratory failure. Crit Care Med. 2021;49:490-502.,2323 Gleissman H, Forsgren A, Andersson E, et al. Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019. Acta Anaesthesiol Scand. 2021;65:360-3.,2626 Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55. Our pooled data showed no significant difference in PaCO2 between the prone and supine groups (MD = 2.45, 95% CI -2.39 to 7.30, p= 0.32; I2= 90%; certainty of evidence = very low, Supplementary Fig. E1). Of all included studies, only one study examined the mortality rate and number of patients discharged alive between the prone and supine groups.2525 Shelhamer M, Wesson PD, Solari IL, et al. Prone positioning in moderate to severe acute respiratory distress syndrome due to COVID-19: a cohort study and analysis of physiology. J Intensive Care Med. 2021;36:241-52. No significant differences were reported in the outcomes of mortality (n = 261 patients, OR = 0.66, 95% CI 0.32 to 1.33, p= 0.24; certainty of evidence = very low, Supplementary Fig. E1) and number of patients discharged alive (n = 261 patients, OR = 1.49, 95% CI 0.72 to 3.08, p= 0.28; certainty of evidence: very low, Supplementary Fig. E1).

Discussion

To the best of our knowledge, this is the first systematic review that has summarized the evidence of prone ventilation in intubated COVID-19 patients during mechanical ventilation. Our systematic review and meta-analysis demonstrated that prone ventilation was associated with higher PaO2/FiO2 ratio and SpO2 than supine ventilation in intubated COVID-19 patients. However, the level of evidence was graded as very low due to the nature of observational studies, inconsistency of substantial heterogeneity, and publication bias. Our findings were consistent with the systematic review and meta-analysis conducted by Munshi and colleagues,55 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:S280-8. which showed that prone positioning during mechanical ventilation in classical ARDS was associated with a significantly higher PaO2/FiO2 ratio on day 4 of intervention. Although most of our included studies reported the PaO2/FiO2 ratio on day 1 of intervention (during the first prone session),1616 Astua AJ, Michaels EK, Michaels AJ. Proning During Pandemic: the rapid institution of a safe, transferable, and effective prone positioning program at Nychhc/elmhurst Hospital, a situationally resource limited facility, during the peak of the Covid 19 surge. Res Sq. 2020.,1717 Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20.,2222 Douglas IS, Rosenthal CA, Swanson DD, et al. Safety and outcomes of prolonged usual care prone position mechanical ventilation to treat acute coronavirus disease 2019 hypoxemic respiratory failure. Crit Care Med. 2021;49:490-502.,2323 Gleissman H, Forsgren A, Andersson E, et al. Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019. Acta Anaesthesiol Scand. 2021;65:360-3.,2626 Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55. it was suggested that the improvement in oxygenation parameters from prone ventilation was reproducible with repeated prone positioning.2727 Kallet RH. A Comprehensive review of prone position in ARDS. Respir Care. 2015;60:1660-87.

Prone ventilation has been widely used during the outbreak of COVID-19 pandemic. Several observational studies reported high frequency use of prone ventilation in intubated COVID-19 patients with ARDS, which ranged from 60% to 79%.2828 Ferrando C, Suarez-Sipmann F, Mellado-Artigas R, et al. Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS. Intensive Care Med. 2020;46:2200-11.

29 Stilma W, van Meenen DMP, Valk CMA, et al. Incidence and practice of early prone positioning in invasively ventilated COVID-19 patients-insights from the PRoVENT-COVID observational study. J Clin Med. 2021;10:4783.

30 Langer T, Brioni M, Guzzardella A, et al. Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients. Crit Care. 2021;25:128.
-3131 and C-IGobotRN, Investigators tC-I. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021;47:60-73. This phenomenon may be explained by a greater predominance of moderate-to-severe hypoxemia among patients with COVID-19 pneumonia, resulting in a drastic rise in the occupancy of intensive care units.3232 Camporota L, Sanderson B, Dixon A, et al. Outcomes in mechanically ventilated patients with hypoxaemic respiratory failure caused by COVID-19. Br J Anaesth. 2020;125:e480-3. Moreover, the adaptation of prone ventilation in COVID-19-related ARDS may have derived from the intervention that had been proven to be beneficial in ARDS of other causes in previous studies.2929 Stilma W, van Meenen DMP, Valk CMA, et al. Incidence and practice of early prone positioning in invasively ventilated COVID-19 patients-insights from the PRoVENT-COVID observational study. J Clin Med. 2021;10:4783. The seminal PROSEVA trial, which showed significant reduction in mortality with prone positioning being applied early in the course of disease (< 24 h) for prolonged periods (> 16 h per session), was likely a fundamental contributing factor.3333 Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368:2159-68.,3434 Sottile PD, Albert RK, Moss M. Prone positioning for nonintubated patients with COVID-19-potential dangers of extrapolation and intermediate outcome variables. JAMA Intern Med. 2022;182:622-3.

In classical ARDS, the development of alveolar flooding with exudates and atelectasis due to inflammatory alveolar injury causes intrapulmonary shunting of blood and hypoxemia.3535 Sweeney RM, McAuley DF. Acute respiratory distress syndrome. Lancet. 2016;388:2416-30. Prone ventilation is believed to reduce the compression on dorsal regions of alveoli by internal organs and ventral regions of the lungs, which occurs in the supine position due to gravity, and helps to even out the transpulmonary pressures across the different regions in the lungs.2727 Kallet RH. A Comprehensive review of prone position in ARDS. Respir Care. 2015;60:1660-87. The improved alveolar recruitment and ventilation-perfusion matching with more homogenous ventilation would benefit patients with severe COVID-19 pneumonia,3636 Santamarina MG, Boisier D, Contreras R, et al. COVID-19: a hypothesis regarding the ventilation-perfusion mismatch. Crit Care. 2020;24:395. and impaired hypoxia-induced pulmonary vasoconstriction and higher incidence of intravascular thrombosis.3737 Grasselli G, Tonetti T, Protti A, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020;8:1201-8. A diverse nature of severe COVID-19 pneumonia can contribute to a substantial degree of heterogeneity. Two recent large, multicenter prospective studies revealed that the form of lung injury in patients with COVID-19-related ARDS was similar to that of classical ARDS, which is characterized by reduced lung compliance and increased lung weight.3737 Grasselli G, Tonetti T, Protti A, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020;8:1201-8.,3838 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;395:1763-70. However, the nature of ARDS itself is a heterogenous syndrome,3939 Wilson JG, Calfee CS. ARDS subphenotypes: understanding a heterogeneous syndrome. Crit Care. 2020;24:102. thus severe COVID-19 induced ARDS patients may respond differently to the effect of prone ventilation.

In this review, most of our included studies recruited COVID-19 patients with PaO2/FiO2 ratio of < 100‒150 mmHg,1616 Astua AJ, Michaels EK, Michaels AJ. Proning During Pandemic: the rapid institution of a safe, transferable, and effective prone positioning program at Nychhc/elmhurst Hospital, a situationally resource limited facility, during the peak of the Covid 19 surge. Res Sq. 2020.

17 Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20.

18 Doussot A, Ciceron F, Cerutti E, et al. Prone positioning for severe acute respiratory distress syndrome in COVID-19 patients by a dedicated team: a safe and pragmatic reallocation of medical and surgical work force in response to the outbreak. Ann Surg. 2020;272:e311-5.
-1919 Abou-Arab O, Haye G, Beyls C, et al. Hypoxemia and prone position in mechanically ventilated COVID-19 patients: a prospective cohort study. Can J Anaesth. 2020;68:262-3.,2121 Berrill M. Evaluation of oxygenation in 129 proning sessions in 34 mechanically ventilated COVID-19 Patients. J Intensive Care Med. 2020;36:229-32.,2222 Douglas IS, Rosenthal CA, Swanson DD, et al. Safety and outcomes of prolonged usual care prone position mechanical ventilation to treat acute coronavirus disease 2019 hypoxemic respiratory failure. Crit Care Med. 2021;49:490-502.,2626 Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55. which corresponded to moderate-to-severe ARDS as defined by the Berlin criteria.4040 Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307: 2526-33. The Berlin criteria, however, did not take lung compliance into consideration. In a study conducted by Puah and colleagues, COVID-19-related ARDS patients with high lung compliance (> 40 mL.cm−1 H2O) on the day of intubation showed significantly higher mortality rates.4141 Puah SH, Cove ME, Phua J, et al. Association between lung compliance phenotypes and mortality in COVID-19 patients with acute respiratory distress syndrome. Ann Acad Med Singap. 2021;50:686-94. Therefore, the great degree of heterogeneity in COVID-19-related ARDS among our included studies could have introduced bias to our findings. Future studies are warranted to examine the use of prone ventilation in a particular subgroup (severe, moderate, or mild) of COVID-19 ARDS patients.

Our included studies, with the exception of the study by Clarke and colleagues, did not report the duration of patients’ illness from the onset of symptoms prior to intubation.1717 Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20. Moreover, it is unknown whether the patients in our included studies were subjected to early or late intervention. The variation in lung compliances in COVID-19 at different timings of intubation may have affected the efficacy of prone ventilation. Pandya and colleagues reported that COVID-19 patients with late intubation (> 1.26 days from time of presentation) had lower lung compliance as compared to those who were intubated earlier.4242 Pandya A, Kaur NA, Sacher D, et al. Ventilatory Mechanics in early vs late intubation in a cohort of coronavirus disease 2019 patients with ARDS. Chest. 2021;159:653-6. Therefore, patients may have responded differently towards prone ventilation at different timepoints during the course of severe COVID-19-related ARDS, and this may have been another source of heterogeneity.

Scholten and colleagues suggested that the clinical benefit of prone positioning ventilation on mortality in ARDS may be related to the attenuation of ventilator-associated lung injury, which stems from the reduction of alveolar hyperinflation in the ventral regions of the lungs during prone ventilation.4343 Scholten EL, Beitler JR, Prisk GK, et al. Treatment of ARDS with prone positioning. Chest. 2017;151:215-24. In our review, however, there was no significant difference in mortality rate and number of patients discharged alive between the prone and supine groups, despite the similarities in ventilation strategy across our included studies. A significant number of patients in our included studies were obese with a mean BMI ranging from 27.9 to 36.5 kg.m−2. A recent review revealed that obesity is associated with increased disease severity in COVID-19 pneumonia.4444 Chu Y, Yang J, Shi J, et al. Obesity is associated with increased severity of disease in COVID-19 pneumonia: a systematic review and meta-analysis. Eur J Med Res. 2020;25: 64. Ni and colleagues showed that obesity was significantly associated with reduced mortality in patients with classical ARDS.4545 Ni YN, Luo J, Yu H, et al. Can body mass index predict clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome? A meta-analysis. Crit Care. 2017;21:36. Thus, our findings cannot be generalized to COVID-19 ARDS patients who are not obese, as obesity contributes to a significant disease burden for patients with multiple comorbidities. In addition, the majority of our included population were elderly patients (> 60 years old). Zhou and colleagues reported that the mortality rate of severe COVID-19 patients was significantly higher with an increased age group.4646 Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62. Nevertheless, our current findings are highly premature in view of the limited number of studies with small sample size.

The fall in PaCO2 indicated an increased removal of carbon dioxide as a result of lung recruitment and reduced fraction of dead-space in patients with ARDS.4747 Vollenberg R, Matern P, Nowacki T, et al. Prone position in mechanically ventilated COVID-19 patients: a multicenter study. J Clin Med. 2021;10:1046. However, our review showed no significant improvement in PaCO2 following the use of prone ventilation in COVID-19 patients. The PaCO2 may decrease, remain unchanged or even increase, depending on the resultant effect of prone position on alveolar ventilation and minute ventilation (the ventilator setting of respiratory rate and tidal volume). Although prone position improves ventilation-perfusion matching in the lungs, it may also reduce chest wall compliance by restricting the movement of the anterior chest wall, and thus limiting carbon dioxide excretion.4848 Guerin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020;46:2385-96. Thus, the effect of prone ventilation on PaCO2 in ARDS has been reported to be inconsistent.

There were several limitations in this review. One of the limitations was the lack of data from randomized controlled trials. Our included studies comprised only retrospective or prospective cohort studies, which contributed to methodological heterogeneity as well as to the low level of evidence. None of the studies reported the complications of both prone and supine ventilation (e.g., pressure ulcers and endotracheal tube obstruction) in COVID-19 patients. Thus, we were unable to assess the safety profile of prone and supine position in the mechanical ventilated COVID-19 patients in this review.

Conclusions

In this meta-analysis, prone ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. However, given the substantial heterogeneity and low level of evidence, more randomized controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.

Acknowledgement

We would like to thank Mr. Bryan Allan for proof-reading the manuscript.

Supplementary materials

Supplementary material associated with this article can be found in the online version at doi:10.1016/j.bjane.2022.06.007.

References

  • 1
    Attaway AH, Scheraga RG, Bhimraj A, et al. Severe covid-19 pneumonia: pathogenesis and clinical management. BMJ. 2021;372:n436.
  • 2
    Meng L, Qiu H, Wan L, et al. Intubation and ventilation amid the COVID-19 outbreak: Wuhan's experience. Anesthesiology. 2020;132:1317-32.
  • 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;323:1574-81.
  • 4
    Auld SC, Caridi-Scheible M, Blum JM, et al. ICU and ventilator mortality among critically Ill adults with coronavirus disease 2019. Crit Care Med. 2020;48:e799-804.
  • 5
    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:S280-8.
  • 6
    Mora-Arteaga JA, Bernal-Ramírez OJ, Rodríguez SJ. The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis. Med Intensiva (Engl Ed). 2015;39:359-72.
  • 7
    WHO. COVID-19 Clinical management: living guidance. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 . [Accessed 1 May 2021]
    » https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
  • 8
    Cardona S, Downing J, Alfalasi R, et al. Intubation rate of patients with hypoxia due to COVID-19 treated with awake proning: a meta-analysis. Am J Emerg Med. 2021;43:88-96.
  • 9
    Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions. Wiley-Blackwell; 2019.
  • 10
    Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
  • 11
    Wan X, Wang W, Liu J, et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.
  • 12
    Wells GA, Shea B, O'Connor D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses. Available from: http://www.ohri.ca/programs/clinica-l_epidemiology/oxford.asp [Accessed 1 May 2021]
    » http://www.ohri.ca/programs/clinica-l_epidemiology/oxford.asp
  • 13
    Khullar R, Shah S, Singh G, et al. Effects of prone ventilation on oxygenation, inflammation, and lung infiltrates in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study. J Clin Med. 2020;9(12):4129.
  • 14
    Mittermaier M, Pickerodt P, Kurth F, et al. Evaluation of PEEP and prone positioning in early COVID-19 ARDS. EClinicalMedicine. 2020;28:100579.
  • 15
    Sang L, Zheng X, Zhao Z, et al. Lung recruitment, individualized PEEP, and prone position ventilation for COVID-19-associated severe ARDS: a single center observational study. Front Med (Lausanne). 2021;7:603943.
  • 16
    Astua AJ, Michaels EK, Michaels AJ. Proning During Pandemic: the rapid institution of a safe, transferable, and effective prone positioning program at Nychhc/elmhurst Hospital, a situationally resource limited facility, during the peak of the Covid 19 surge. Res Sq. 2020.
  • 17
    Clarke J, Geoghegan P, McEvoy N, et al. Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients. BMC Res Notes. 2021;14:20.
  • 18
    Doussot A, Ciceron F, Cerutti E, et al. Prone positioning for severe acute respiratory distress syndrome in COVID-19 patients by a dedicated team: a safe and pragmatic reallocation of medical and surgical work force in response to the outbreak. Ann Surg. 2020;272:e311-5.
  • 19
    Abou-Arab O, Haye G, Beyls C, et al. Hypoxemia and prone position in mechanically ventilated COVID-19 patients: a prospective cohort study. Can J Anaesth. 2020;68:262-3.
  • 20
    Perier F, Tuffet S, Maraffi T, et al. Effect of positive end-expiratory pressure and proning on ventilation and perfusion in COVID-19 acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;202:1713-7.
  • 21
    Berrill M. Evaluation of oxygenation in 129 proning sessions in 34 mechanically ventilated COVID-19 Patients. J Intensive Care Med. 2020;36:229-32.
  • 22
    Douglas IS, Rosenthal CA, Swanson DD, et al. Safety and outcomes of prolonged usual care prone position mechanical ventilation to treat acute coronavirus disease 2019 hypoxemic respiratory failure. Crit Care Med. 2021;49:490-502.
  • 23
    Gleissman H, Forsgren A, Andersson E, et al. Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019. Acta Anaesthesiol Scand. 2021;65:360-3.
  • 24
    Sharp T, Al-Faham Z, Brown M, et al. Prone position in covid-19: can we tackle rising dead space?J Intensive Care Soc. 2020;0:1-4.
  • 25
    Shelhamer M, Wesson PD, Solari IL, et al. Prone positioning in moderate to severe acute respiratory distress syndrome due to COVID-19: a cohort study and analysis of physiology. J Intensive Care Med. 2021;36:241-52.
  • 26
    Weiss TT, Cerda F, Scott JB, et al. Prone positioning for patients intubated for severe acute respiratory distress syndrome (ARDS) secondary to COVID-19: a retrospective observational cohort study. Br J Anaesth. 2020;126:48-55.
  • 27
    Kallet RH. A Comprehensive review of prone position in ARDS. Respir Care. 2015;60:1660-87.
  • 28
    Ferrando C, Suarez-Sipmann F, Mellado-Artigas R, et al. Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS. Intensive Care Med. 2020;46:2200-11.
  • 29
    Stilma W, van Meenen DMP, Valk CMA, et al. Incidence and practice of early prone positioning in invasively ventilated COVID-19 patients-insights from the PRoVENT-COVID observational study. J Clin Med. 2021;10:4783.
  • 30
    Langer T, Brioni M, Guzzardella A, et al. Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients. Crit Care. 2021;25:128.
  • 31
    and C-IGobotRN, Investigators tC-I. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021;47:60-73.
  • 32
    Camporota L, Sanderson B, Dixon A, et al. Outcomes in mechanically ventilated patients with hypoxaemic respiratory failure caused by COVID-19. Br J Anaesth. 2020;125:e480-3.
  • 33
    Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368:2159-68.
  • 34
    Sottile PD, Albert RK, Moss M. Prone positioning for nonintubated patients with COVID-19-potential dangers of extrapolation and intermediate outcome variables. JAMA Intern Med. 2022;182:622-3.
  • 35
    Sweeney RM, McAuley DF. Acute respiratory distress syndrome. Lancet. 2016;388:2416-30.
  • 36
    Santamarina MG, Boisier D, Contreras R, et al. COVID-19: a hypothesis regarding the ventilation-perfusion mismatch. Crit Care. 2020;24:395.
  • 37
    Grasselli G, Tonetti T, Protti A, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020;8:1201-8.
  • 38
    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;395:1763-70.
  • 39
    Wilson JG, Calfee CS. ARDS subphenotypes: understanding a heterogeneous syndrome. Crit Care. 2020;24:102.
  • 40
    Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307: 2526-33.
  • 41
    Puah SH, Cove ME, Phua J, et al. Association between lung compliance phenotypes and mortality in COVID-19 patients with acute respiratory distress syndrome. Ann Acad Med Singap. 2021;50:686-94.
  • 42
    Pandya A, Kaur NA, Sacher D, et al. Ventilatory Mechanics in early vs late intubation in a cohort of coronavirus disease 2019 patients with ARDS. Chest. 2021;159:653-6.
  • 43
    Scholten EL, Beitler JR, Prisk GK, et al. Treatment of ARDS with prone positioning. Chest. 2017;151:215-24.
  • 44
    Chu Y, Yang J, Shi J, et al. Obesity is associated with increased severity of disease in COVID-19 pneumonia: a systematic review and meta-analysis. Eur J Med Res. 2020;25: 64.
  • 45
    Ni YN, Luo J, Yu H, et al. Can body mass index predict clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome? A meta-analysis. Crit Care. 2017;21:36.
  • 46
    Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.
  • 47
    Vollenberg R, Matern P, Nowacki T, et al. Prone position in mechanically ventilated COVID-19 patients: a multicenter study. J Clin Med. 2021;10:1046.
  • 48
    Guerin C, Albert RK, Beitler J, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020;46:2385-96.

Publication Dates

  • Publication in this collection
    14 Oct 2022
  • Date of issue
    Nov-Dec 2022

History

  • Received
    12 Nov 2021
  • Accepted
    21 June 2022
Sociedade Brasileira de Anestesiologia (SBA) Rua Professor Alfredo Gomes, 36, Botafogo , cep: 22251-080 - Rio de Janeiro - RJ / Brasil , tel: +55 (21) 97977-0024 - Rio de Janeiro - RJ - Brazil
E-mail: editor.bjan@sbahq.org