Prone vs supine position in intubated COVID-19 patients with ARDS: a systematic review and meta-analysis

Dita Aditianingsih1, Adhrie Sugiarto2, Sidharta Kusuma Manggala3, Hansen Angkasa4, Ahmad Pasha Natanegara5
Author affiliation:
  1. Dita Aditianingsih, Intensive Care Consultant, Cipto Mangunkusumo Hospital, Pangeran Diponegoro Street No. 71, Kenari, Central Jakarta City, Indonesia; E-mail: ditaaditiaa@gmail.com
  2. Adhrie Sugiarto, Intensive Care Consultant, Cipto Mangunkusumo Hospital, Pangeran Diponegoro Street No. 71, Kenari, Central Jakarta City, Indonesia; E-mail: adhrie@gmail.com
  3. Sidharta Kusuma Manggala, Intensive Care Consultant, Cipto Mangunkusumo Hospital, Pangeran Diponegoro Street No. 71, Kenari, Central Jakarta City, Indonesia; E-mail: maninjau3@gmail.com
  4. Hansen Angkasa, Medical Officer, Cipto Mangunkusumo Hospital, Pangeran Diponegoro Street No. 71, Kenari, Central Jakarta City, Indonesia; E-mail: dr.h.angkasa@gmail.com
  5. Ahmad Pasha Natanegara, Medical Officer, Cipto Mangunkusumo Hospital, Pangeran Diponegoro Street No. 71, Kenari, Central Jakarta City, Indonesia; E-mail: pasha.natanegara@gmail.com
Correspondence: Dita Aditianingsih, E-mail: ditaaditiaa@gmail.com; Phone: +628151819244

 

ABSTRACT

 

Background & Objective: The recent COVID-19 pandemic has tested the healthcare sector to the maximum, but it also has taught us some valuable lessons, especially in the context of intensive care, and particularly in the respiratory support. This review determined the effect of prone positioning in changes of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, partial pressure of carbon dioxide (PaCO2), mortality rate, ICU length of stay and duration of mechanical ventilation in intubated COVID-19 patients with ARDS.

Methodology: A computer-aided comprehensive electronic bibliographic search from MEDLINE, EMBASE, and Science Direct were conducted. The search comprised the articles written in English and intubated adult (≥ 18 y old) patients with COVID-19. The primary outcome was comparing PaO2/FiO2 ratio between prone and supine position groups. Secondary outcomes were comparisons of PaCO2, ICU discharge, and mortality rate. Review Manager version 5.4 (The Cochrane Collaboration) was used for statistical analyses of the included studies.

Results: A total of 7 articles were determined to be eligible, consisting of 1403 intubated COVID-19 patients with ARDS that showed prone position was associated with a higher PaO2/FiO2 ratio compared to the supine position (MD 60.17, 95% CI 46.86−73.47; P < 0.00001). Four studies reported the PaCO2 measurements and showed no significant difference between prone and supine positions (MD 2.07, 95% CI -2.79−6.92; P < 0.40). Only two studies reported mortalities, one study had 262 deaths out of 648 patients (40.4%) and the other study lost 11 out of 20 patients (55%). One study reported median ICU stay and mechanical ventilation duration (16 days) were significantly longer in prone position group.

Conclusion: This meta-analysis showed that prone position improved PaO2/FiO2 ratio in intubated COVID-19 patients with ARDS. It also prolonged ICU stay and mechanical ventilation duration, but had no effect on mortality rate.

Abbreviations: APACHE-II- Acute Physiology and Chronic Health Evaluation-II; ARDS - acute respiratory distress syndrome; ICU – Intensive Care Unit; MD – Mean Difference; NOS - Newcastle-Ottawa scale; SOFA - Sequential Organ Failure Assessment

Key words: Prone Position; Supine Position; COVID-19; ARDS, Intubation; Meta-Analysis

Citation: Aditianingsih D, Sugiarto A, Manggala SK, Angkasa H, Natanegara AP. Prone versus supine position in intubated COVID-19 patients with ARDS: a systematic review and meta-analysis. Anaesth. pain intensive care 2023;27(4):535−544; DOI: 10.35975/apic.v27i4.2136
Received: January 20, 2023; Reviewed: May 04, 2023; Accepted: June 23, 2023

 

1. INTRODUCTION

 

The World Health Organization (WHO) declared a public health emergency on coronavirus disease 2019 (COVID-19), a global pandemic that impacted more than 200 countries and caused over 3.9 million deaths.1 As of July 2021, there were 2.35 million COVID-19 cases in Indonesia with 61.868 reported deaths.2 Approximately 67–85% of critically ill patients who were admitted to the intensive care unit (ICU) with COVID-19 developed hypoxemia, acute respiratory distress syndrome (ARDS) that required intubation and the mechanical ventilation.3 It is well-known that respiratory failure with ARDS has poor outcomes; and COVID-19 patients with ARDS are no exception.4 Some countries reported 61.5% fatality rate, especially those on mechanical ventilation.5 In the United Kingdom, 4855 patients with COVID-19 needed advance respiratory support and 57% of them died.6
Over the last decades, ARDS interventions have been evaluated, in particular, prone position was an important non-pharmacologic strategy that showed lifesaving potential for invasively ventilated patients with moderate to severe ARDS.7 Placing the patient in prone position optimizes the ventilation and decreases the intrapulmonary shunting which facilitates more effective oxygenation due to more uniform alveolar recruitment throughout the lung.8 A meta-analysis of prone position in ARDS and acute lung injury showed that prone position during invasive mechanical ventilation improved oxygenation and reduced ICU mortality rate.9 The Surviving Sepsis Campaign (SSC) COVID-19 subcommittee and WHO guidelines have recommend prone position for the management of COVID-19 associated ARDS.10, 11 Recently, a hypothesis emerged stating that ARDS due to COVID-19 was different than non-COVID-19 ARDS whose features were severe hypoxemia with normal respiratory system compliance.12 Gattinoni et al. suggested that there are two phenotypes of COVID-19 ARDS, which were “type L”, characterized by low elastance, low ventilation-to-perfusion (V/Q) ratio, low lung weight, and low recruitability, and “type H”, characterized by high elastance, high right-to-left shunt, high lung weight, and high lung recruitability (which was similar to non-COVID-19 ARDS).12, 13
Several studies have suggested the need of outcome measurements after prone position maneuver for mechanically ventilated COVID-19 patients. Currently, there are very limited studies comparing prone position and supine position in intubated COVID-19 patients. The aim of this analysis was to determine the changes of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio after prone position compared to supine position in intubated COVID-19 patients with ARDS. This review also examines the changes of partial pressure of carbon dioxide (PaCO2), mortality rate, duration of mechanical ventilation and ICU length of stay.

 

2. METHODOLOGY

 

2.1. Search Strategy
This systematic review was conducted according to the PRISMA statement.14 A computer-aided comprehensive electronic bibliographic search from MEDLINE, EMBASE, and ScienceDirect were conducted on the July 07, 2021, for articles published in the last 10 y (July 07, 2011−July 07, 2021). A grey literature search was not conducted. Boolean phrase, medical subject headings (MeSH), and truncations were used when searching each database. Multiple searches were conducted to ensure all relevant studies were identified. A manual search of the reference list from the articles retrieved for additional relevant studies was also undertaken. The keywords and terms used for the search were “COVID#19”, “coronavirus disease 2019”, “acute respiratory distress syndrome”, “ARDS”, “intubated”, “prone position”, “supine position”, “prone*”, “TI prone position”, “AB prone position”, “COVID#19 OR acute respiratory distress syndrome”, “coronavirus disease 2019 OR acute respiratory distress syndrome”, “COVID#19 OR ARDS”, “coronavirus disease OR ARDS”, “COVID#19 OR TI COVID#19”, “COVID#19 OR intubated OR ARDS”, “(COVID#19 OR intubated OR ARDS) AND prone position”. The review was not registered.

Intubated COVID-19 patients were determined as the population, prone position as the intervention, supine position as the comparison and PaO2/FiO2 ratio, PaCO2, mortality rate, ICU discharge, and duration of mechanical ventilation as the outcome. Potentially relevant articles from the three databases were included. The potential articles then were removed or excluded through a manually-systematic search of duplicate articles and a screening based on the title and abstract. The full-text of the remaining articles was examined based on the predefined review criteria and the remaining articles were included in the review. Two authors screened titles and abstracts independently based on the inclusion and exclusion criteria. Studies that met the criteria were coded with “yes” and were retrieved for full text screening. Studies coded with “no” were excluded from the review. Two authors independently screened the full text articles and finally included studies were approved by all authors.

 

2.2. Review Criteria
Included studies comprised of articles that was written in English, any other language was not included in the review. The subjects being human, adults (≥ 18 y old) diagnosed with COVID-19, intubated, comparing prone position and supine position, and measure the following outcomes: 1) PaO2/FiO2 ratio, 2) PaCO2, 3) mortality rate, 4) duration of mechanical ventilation, and 5) ICU length of stay. Systematic reviews and meta-analyses were excluded from the review, as well as the case reports. Other exclusion criteria were case series, editorials, and non-intubated (using high flow nasal cannula or non-invasive ventilation) patients.

 

2.3. Data Extraction
Two independent authors extracted data from the included articles. The data extracted were the type of interventions being compared (prone and supine position), outcome measures, including PaO2/FiO2 ratio (ratio of the first prone change), PaCO2, mortality rate, ICU discharge, and duration of mechanical ventilation. Other data such as year of publication, study design, sample size, mean age, severity by Acute Physiology and Chronic Health Evaluation-II (APACHE-II) and Sequential Organ Failure Assessment (SOFA) score, and duration of prone position were also extracted.

Review Manager version 5.4 (The Cochrane Collaboration) was used for statistical analyses. A two-sided P < 0.05 was denoted as statistically significant. For dichotomous outcomes, odds ratio (OR) was used, while for continuous outcomes, mean difference (MD), along with 95% confidence interval (CI) was used.

I2 of less than 40% was considered insignificant, 40–60% was considered moderate heterogeneity, and more than 60% were categorized as substantial heterogeneity.16
 



 

2.4. Quality Assessment
The qualities of the studies included were independently assessed using Cochrane Risk of Bias Tool for randomized controlled trials (RCTs).17 The tool examines 7 distinct domains, including randomization procedures, blindinmethods, and appropriate data reporting. Points are only rewarded when a criterion is fulfilled. All criteria were scored by the basis of ‘High risk of bias’ (-), ‘Low risk of bias’ (+), and ‘Unclear risk of bias’ (?). For non-RCTs, we used Newcastle Ottawa Scale (NOS).18 NOS examines three categories, which are Selection, Comparability, and Outcome for cohort studies. While for case-control studies Exposure was examined instead of Outcome. The maximum score a study can obtain was 9. In the cohort segment, a maximum of 1 star for each question within the Selection and Outcome categories and a maximum of 2 stars can be given for Comparability. Meanwhile in the case-control segment, a maximum of 1 star for each question within the Selection and Exposure categories and a maximum of 2 stars for Comparability can be awarded. The cut-off to consider a study for low risk of bias was ≥7, the same as previous studies. GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach was used to examine the certainty of evidence and was conducted by two authors independently.

 

Table 1: Quality Assessment of Included Cohort Studies: Newcastle-Ottawa Criteria
Study Selection Comparability Outcome Total Score Overall risk of bias
Astua et al. **** ** ** ******** 8 Low
Berrill et al. **** ** ** ********* 9 Low
Mittermaier et al. **** ** ** ******** 8 Low
Weiss et al. **** ** *** ********* 9 Low
Gleissman et al. **** ** ** ******** 8 Low
Clarke et al. **** ** ** ******** 8 Low
Langer et al. **** ** ** ******** 8 Low
 

3. RESULTS

 

3.1. Search Findings
The combined search using MEDLINE, EMBASE and Science Direct was conducted from July 07, 2019 –July 07, 2021. The search yielded 1,729 published studies. Based on the titles, abstract, and duplicates screened, 852 potential articles remained and full-text articles were retrieved out of them. The full-text articles were reviewed based on eligibility criteria, a total of 7 articles were determined to be eligible for inclusion in this eview (Figure 1). All of the studies were quality assessed using the Newcastle-Ottawa scale (NOS) and had low risk of bias (Table 1).

The combined search using MEDLINE, EMBASE and Science Direct was conducted from July 07, 2019 –July 07, 2021. The search yielded 1,729 published studies. Based on the titles, abstract, and duplicates screened, 852 potential articles remained and full-text articles were retrieved out of them. The full-text articles were reviewed based on eligibility criteria, a total of 7 articles were determined to be eligible for inclusion in this eview (Figure 1). All of the studies were quality assessed using the Newcastle-Ottawa scale (NOS) and had low risk of bias (Table 1).

 

3.2. Characteristics of the included articles
The seven studies included in this review were cohort studies (Table 2).19-25 All of the studies were quality assessed using NOS and had low risk of bias (Table 2). The sample size varied in between a study having only 9 subjects and another having 648, which was a multi-centered study. We could not find any randomized controlled trials in this area.

All the recruited COVID-19 patients were from ICUs where the participants were mechanically ventilated. The mean age of all of the included studies ranged between 53 and 63 y. Three included studies calculated APACHE II score during the first 24 h of ICU admission, two of the studies calculated both APACHE II and SOFA scores. Furthermore, two other studies only used SOFA and two studies did not use either of the two scales. The APACHE II varied from an average of 10 to 26.2 and SOFA score ranged from 6.8 to 8.2. The duration of prone position sessions was similar across seven studies, averaging around 16 h of prone position. The studies recorded PaO2/FiO2 ratio on supine position, ranging from a mean of 17.5 as the lowest and 123 as the highest. All the studies included adult (18−75 y of age) COVID-19 patients, confirmed by laboratory results, with ARDS as defined by Berlin criteria, and were mechanically ventilated. Three studies mentioned PaO2/FiO2 ratio and had a similar cut-off, which was ≤ 150 mmHg and FiO2 ≤ 0.6.

 



 



 



 

3.3. Outcome measures
The combined data of seven studies, consisting of 1403 COVID-19 patients who had severe ARDS and were intubated, showed that prone position group was associated with higher PaO2/FiO2 ratio compared to supine position group (MD 60.17, 95% CI 46.86 to 73.47; P < 0.00001; Figure 2). The statistical heterogeneity was observed to be extensive (I2 = 87%) and the funnel plot resulted in asymmetrical shape, suggestive of publication bias (Figure 3).

Four studies reported the PaCO2 measurement during prone position and supine position with 1331 patients combined. It showed no significant difference between prone position and supine position (MD 2.07, 95% CI -2.79 to 6.92; P < 0.40; Figure 4). Heterogeneity was observed as substantial (I2 = 95%). Quality of evidence using GRADE approach was found to be very low for both analysis (Table 3).

Out of seven studies, only two studies mentioned mortalities whereas five other studies did not report. Langer et al. had 262 deaths out of 648 patients (40.4%) and Weiss et al. lost 11 out of 20 patients (55%). In addition, this study reported mechanical ventilation duration with median of 16 days (interquartile range 10-30) were significantly longer in prone position group compared to supine position group. 23,25
Two studies by Langer et al. and Mittermaier et al. displayed ICU length of stay.23, 24 However, Mittermaier et al. did not compare between prone position and supine      position. The study analyzed 23 samples and divided into 3 subgroups, one of which was prone position analysis. There was overlapping of samples between the subgroups. The average length of stay (in days) was 50.4 with standard deviation of 34.9. One study compared the two groups and reported that patients in prone position had a significantly longer stay in the ICU with median of 16 days (IQR 11−28).

 

4. DISCUSSION

 

This study demonstrated that COVID-19 patients with ARDS were associated with a higher PaO2/FiO2 ratio in the prone position group compared to supine position group. The findings of this meta-analysis agree with prior studies, suggesting that prone positioning may improve oxygenation of injured lungs. The included articles were all cohorts, as there are no randomized controlled trials (RCTs) available, and were quality assessed using NOS which seven of the studies had a low risk of bias. However, the heterogeneity was substantial, and the funnel plot suggested publication bias.

 

Table 3: Certainty assessment using GRADE approach
Studies Design No. of patients Risk of bias Inconsistency Indirectness Imprecision Publication bias Effect
(95% CI)		 Certainty
PP SP
PaO2/FiO2 Cohort 828 575 Not serious Substantial a Not serious Not serious Very serious b MD 60.17

[46.86−73.47]		 Very low
PaCO2 Cohort 785 546 Not serious Substantial a Not serious Not serious Very serious b MD 2.07

[-2.79−6.92]		 Very low
Results of 5 studies; CI: Confidence interval; MD: Mean difference; a Substantial heterogeneity
b Funnel plot suggested of publication bias 
 



 

The PaO2/FiO2 ratio is an integral component to diagnose ARDS. It is one of the key parameters in the Berlin criteria.26 The severity of the disease can be based on the ratio starting from 200−300 mmHg as mild, 100−200 as PaO2/FiO2 levels, thus, making it become a valuable diagnostic, prognostic and clinical management tool.27
Several studies have proven that prone position helped improve the ventilation-perfusion ratio due to expansion of the collapsed dorsal lung, reduction of the pleural distribution of the lung stress and strain.25,28 The PROSEVA study concluded that the 28-day mortality for severe ARDS patients assigned to prone position group was 16% and the unadjusted 90-day mortality was 23.6% compared to those in supine position, where the figures were 32.8% and 41% respectively.29 However, post hoc analysis suggested that, although there was a substantial improvement of gas exchange and reduction of mortality, there was no association between them.30 Nonetheless, newer studies have contradicted this result. Park et al. found that oxygenation improvement of COVID-19 ARDS after prone position was associated with clinical outcomes.31 Another study by Camporota and team also found that there was a significant oxygenation response of patients with COVID-19 ARDS and was associated with improved survival.32 Since the pandemic began large numbers of hospitalized COVID-19 patients fulfilled the criteria of ARDS, which required invasive mechanical ventilation and a high level of patient care.2,6,19 Numerous studies recommended prone positioning to help improve oxygenation and decrease work of breathing.

Additionally, this review also examined PaCO2 levels between the two groups and found that there was no significant association between the prone position with PaCO2 level which was contradicts the prior studies.29,33-36 Altered ventilation-perfusion ratio is a fundamental cause of abnormal gas exchange, which a low ratio induces hypoxemia and a high ratio induces hypercapnia.33 Under normal physiology, PaCO2 is the primary control for air exchange, specifically for the minute ventilation or amount of air exchanged in the lungs per minute.28,34 It is responsible for affecting the pH; if there is an increase in PaCO2 then the pH will decrease and increase minute ventilation. Whereas, a decrease in PaCO2 will increase pH and decrease minute ventilation.29, 35 A study conducted in 2003 by Gattinoni et al. showed a reduction of PaCO2 level in ARDS patients in response to prone position.13 It stated that prone positioning reduced areas of distended lungs and the physiological dead-space, therefore it reduced shunts and resulted in reduction in PaCO2.36 We included four cohort studies with low risk of bias to measure the outcome in PaCO2 level, and found the heterogeneity was extensive. The possible mechanism that prone position did not significantly affect the level of PaCO2 was prone position using pressure-controlled ventilation would have a reduction of the chest wall compliance that reduced the tidal volume and minute ventilation.37 Furthermore, prone position using volume-controlled ventilation would have the increased pleural pressure that reduced the venous return and affected the regional perfusion and increased the dead space.37 Langer and colleague called it the CO2-non responders.24
Two articles mentioned mortality, Weiss et al. showed 55% and Langer et al. showed 40.4% of patients died in their study.23,25 Furthermore, Langer et al. compared mortality between prone position versus supine position group and reported that 112/409 (28%) patients died in the supine position group.24,25 However, the significance was not calculated by the author.

Langer et al. compared ICU length of stay between the groups. For ICU length of stay, prone position patients had a significantly longer median of 16 days (IQR 11−28) compared to median 12 days (IQR 7−21) for the supine position group. This result supported other studies suggesting that prone positioning had longer time to death and in parallel to the beneficial changes of physiological parameters such as PaO2/FiO2 ratio.38-41 The mechanical ventilation duration was also significantly longer in prone position group compared to supine position group.23 The result might represent that prone positioning was applied as a salvage procedure on ARDS patients with more severe conditions. Another included study mentioned ICU length of stay with an average of 50.4 days.24 However, Mittermaier et al. did not compare between prone position and supine position.24 The study analyzed 23 samples and divided into 3 subgroups, one of which was about prone position analysis. There were overlapping of samples between the subgroups, therefore, no direct comparison of prone position and supine position can be made. Thus, analysis of results from Langer and Mittermaier could not be performed.

 

5. LIMITATIONS

 

All trials included in this review were observational studies in nature, while RCT studies were not yet available. Other limitations were the high degree in heterogeneity, risk of publication bias, no standardized prone position protocol, and the certainty of the measured outcome was very low.

 

6. CONCLUSION

 

Based on the results obtained from this meta-analysis, it can be concluded that intubated COVID-19 patients with ARDS had better PaO2/FiO2 ratio when in prone position. We found that there was no difference for PaCO2 in prone position. Other outcomes such as mortality rate, ICU length of stay, and mechanical ventilation days could not be determined. Due to the limited number of studies with small sample size, high heterogeneity of measured outcomes, and very low certainty of evidence, further randomized clinical studies are needed.

7. Availability of data
All data generated or analyzed during this study are included in this published article [and its supplementary information files].

8. Acknowledgments
We would like to thank Fathimah Azzahra for her effort in proof-reading our manuscript.

9. Competing interests
The authors declare that they have no competing interests. No external or industry funding was involved in this study. applicable.

10. Authors’ contribution
DA, AS. SKM: Conceptualization; Data curation; Methodology; Project administration; Formal analysis; Writing - original draft; Supervision; Validation; Visualization; Writing - review & editing; Investigation.

HA, APN: Data curation; Investigation; Methodology; Software; Visualization; Writing - original draft; Writing - review & editing.

 

REFERENCES

 
  1. Organization WH. WHO Coronavirus disease (COVID-19) dashboard; 2020. Available from: https://covid19.who.int/
  2. University JH. Mortality Analyses – John Hopkins Coronavirus Resource Center; 2020. Available from: https://coronavirus.jhu.edu/data/mortality
  3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. [PubMed] DOI: 1016/S0140-6736(20)30183-5
  4. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788-800. [PubMed] DOI: 1001/jama.2016.0291
  5. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-81. [PubMed] DOI: 1016/S2213-2600(20)30079-5
  6. Centre ICNAR. COVID19 report; 2020. Available from: https://www.icnarc.org/our-audit/audits/cmp/reports
  7. Kallet RH. A Comprehensive Review of Prone Position in ARDS. Respir Care. 2015 Nov;60(11):1660-87. [PubMed] DOI: 4187/respcare.04271
  8. Flynn Makic MB. Prone Position of Patients With COVID-19 and Acute Respiratory Distress Syndrome. J Perianesth Nurs. 2020 Aug;35(4):437-438. [PubMed] DOI: 1016/j.jopan.2020.05.008
  9. Abroug F, Ouanes-Besbes L, Dachraoui F, Ouanes I, Brochard L. An updated study-level meta-analysis of randomised controlled trials on proning in ARDS and acute lung injury. Crit Care. 2011;15(1):R6. [PubMed] DOI: 1186/cc9403
  10. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-887. [PubMed] DOI: 1007/s00134-020-06022-5
  11. Organization WH. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance; 2020. Available from: https://apps.who.int/iris/handle/10665/330893
  12. Beloncle F, Studer A, Seegers V, Richard JC, Desprez C, Fage N, et al. Longitudinal changes in compliance, oxygenation and ventilatory ratio in COVID-19 versus non-COVID-19 pulmonary acute respiratory distress syndrome. Crit Care. 2021 Jul 15;25(1):248. [PubMed] DOI: 1186/s13054-021-03665-8
  13. Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. [PubMed] DOI: 1007/s00134-020-06033-2
  14. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009 Jul 21;6(7):e1000100. [PubMed] DOI: 1371/journal.pmed.1000100
  15. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014 Dec 19;14:135. [PubMed] DOI: 1186/1471-2288-14-135
  16. Higgins JPT. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.1. London, UK: Cochrane; 2020.
  17. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011 Oct 18;343:d5928. [PubMed] DOI: 1136/bmj.d5928
  18. Hospital TO. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
  19. 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. Research Square; 2020. DOI: 21203/rs.3.rs-29653/v1
  20. Berrill M. Evaluation of Oxygenation in 129 Proning Sessions in 34 Mechanically Ventilated COVID-19 Patients. J Intensive Care Med. 2021 Feb;36(2):229-232. [PubMed] DOI: 1177/0885066620955137
  21. Clarke J, Geoghegan P, McEvoy N, Boylan M, Ní Choileáin O, Mulligan M, 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 Jan 9;14(1):20. [PubMed] DOI: 1186/s13104-020-05426-2
  22. Gleissman H, Forsgren A, Andersson E, Lindqvist E, Lipka Falck A, Cronhjort M, et al. Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019. Acta Anaesthesiol Scand. 2021 Mar;65(3):360-363. [PubMed] DOI: 1111/aas.13741
  23. Langer T, Brioni M, Guzzardella A, Carlesso E, Cabrini L, Castelli G, et al. Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients. Crit Care. 2021 Apr 6;25(1):128. [PubMed] DOI: 1186/s13054-021-03552-2
  24. Mittermaier M, Pickerodt P, Kurth F, De Jarcy LB, Uhrig A, Garcia C, et al. Evaluation of PEEP and prone positioning in early COVID-19 ARDS. EClinicalMedicine. 2020;28:100579. [PubMed] DOI: 1016/j.eclinm.2020.100579
  25. Weiss TT, Cerda F, Scott JB, Kaur R, Sungurlu S, Mirza SH, 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. 2021 Jan;126(1):48-55. [PubMed] DOI: 1016/j.bja.2020.09.042
  26. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. [PubMed] DOI: 1001/jama.2012.5669
  27. Villar J, Pérez-Méndez L, Blanco J, Añón JM, Blanch L, Belda J, et al. A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting--a prospective, multicenter validation study. Intensive Care Med. 2013 Apr;39(4):583-92. [PubMed] DOI: 1007/s00134-012-2803-x
  28. Scholten EL, Beitler JR, Prisk GK, Malhotra A. Treatment of ARDS With Prone Positioning. Chest. 2017;151(1):215-24. [PubMed] DOI: 1016/j.chest.2016.06.032
  29. Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2013;368(23):2159-68. [PubMed] DOI: 1056/NEJMoa1214103
  30. Albert RK, Keniston A, Baboi L, Ayzac L, Guérin C. Prone Position–induced Improvement in Gas Exchange Does Not Predict Improved Survival in the Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2014 Feb 15;189(4):494-6. [PubMed] DOI: 1164/rccm.201311-2056LE
  31. Park J, Lee HY, Lee J, Lee SM. Effect of prone positioning on oxygenation and static respiratory system compliance in COVID-19 ARDS vs. non-COVID ARDS. Respir Res. 2021 Aug 6;22(1):220. [PubMed] DOI: 1186/s12931-021-01819-4
  32. Camporota L, Sandersen B, Chiumello D, Terzi N, Argaud L, Rimmele T, et al. Prone Position in Coronavirus Disease 2019 and Noncoronavirus Disease 2019 Acute Respiratory Distress Syndrome: An International Multicenter Observational Comparative Study. Crit Care Med. 2022 Apr 1;50(4):633-643. [PubMed] DOI: 1097/CCM.0000000000005354
  33. Radermacher P, Maggiore SM, Mercat A. Fifty Years of Research in ARDS. Gas Exchange in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017 Oct 15;196(8):964-984. [PubMed] DOI: 1164/rccm.201610-2156SO
  34. Malinoski DJ, Todd SR, Slone S, Mullins RJ, Schreiber MA. Correlation of central venous and arterial blood gas measurements in mechanically ventilated trauma patients. Arch Surg. 2005 Nov;140(11):1122-5. [PubMed] DOI: 1001/archsurg.140.11.1122
  35. Byrne AL, Bennett M, Chatterji R, Symons R, Pace NL, Thomas PS. Peripheral venous and arterial blood gas analysis in adults: are they comparable? A systematic review and meta-analysis. Respirology. 2014;19(2):168-75. [PubMed] DOI: 1111/resp.12225
  36. Gattinoni L VF, Carlesso E, Taccone P, Conte V, Chiumello D, et al. Decrease in paco2 with prone position is predictive of improved outcome in acute respiratory distress. Crit Care Med. 2003;31(12):2727-33. [PubMed] DOI: 1097/01.CCM.0000098032.34052.F9
  37. Guérin C, Albert RK, Beitler J, Gattinoni L, Jaber S, Marini JJ, et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med. 2020 Dec;46(12):2385-2396. [PubMed] DOI: 1007/s00134-020-06306-w
  38. Shelhamer MC, Wesson PD, Solari IL, Jensen DL, Steele WA, Dimitrov VG, 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 Feb;36(2):241-252. [PubMed] DOI: 1177/0885066620980399
  39. Caputo ND, Strayer RJ, Levitan R. Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED's Experience During the COVID-19 Pandemic. Acad Emerg Med. 2020 May;27(5):375-378. [PubMed] DOI: 1111/acem.13994
  40. Carsetti A, Damia Paciarini A, Marini B, Pantanetti S, Adrario E, et al. Prolonged prone position ventilation for SARS-CoV-2 patients is feasible and effective. Crit Care. 2020 May 15;24(1):225. [PubMed] DOI: 1186/s13054-020-02956-w
  41. 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 Jan 30;24(1):28. [PubMed] DOI: 1186/s13054-020-2738-5