Scientific letter
Analytic review and meta-analysis of awake prone positioning in patients with Covid-19
Revisión analítica y meta-análisis de prono vigil en pacientes con Covid-19
R. Santa Cruza,b,
, C. Irrazábalc, L. Gonzalezb, A. Gelosoa, C. Nuñezb, R. Cornejod
Autor para correspondencia
a Department of Intensive Care, Hospital Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina
b Laboratory of Physiology, School of Medicine, University of Magallanes, Punta Arenas, Chile
c Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
d Unidad de Pacientes Críticos, Departamento de Medicina, Hospital Clínico Universidad de Chile, Chile
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"apellidos" => "Santa Cruz" "email" => array:1 [ 0 => "resc.hrrg@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C." "apellidos" => "Irrazábal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "L." "apellidos" => "Gonzalez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Geloso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "C." "apellidos" => "Nuñez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "R." "apellidos" => "Cornejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Intensive Care, Hospital Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Laboratory of Physiology, School of Medicine, University of Magallanes, Punta Arenas, Chile" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital de Clínicas José de San Martín, Buenos Aires, Argentina" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad de Pacientes Críticos, Departamento de Medicina, Hospital Clínico Universidad de Chile, Chile" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Revisión analítica y meta-análisis de prono vigil en pacientes con Covid-19" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 783 "Ancho" => 2917 "Tamanyo" => 201136 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Intubation rate. Forest plot of comparisons between APP and UC.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">SARS-CoV-2 virus (Covid-19) is an infectious disease where most cases have mild symptoms, while few have pneumonia with respiratory failure. Because prone positioning (PP) improves survival in patients with acute respiratory distress syndrome (ARDS), its use has been recommended in Covid-19 patients. PP has shown more homogenous distribution of ventilation and decreasing shunt in dorsal regions and dead space in ventral regions in mechanically ventilated COVID-19 patients. However, the impact of PP in awake patients has not been well defined. Our aim was to perform a meta-analysis to assess the impact of awake prone positioning (APP) on intubation rate, mortality and gas exchange in Covid-19.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A systematic search was performed in MEDLINE, CENTRAL, Web of Science and Lilacs on August 20th, 2021. We used a strategy that combined keywords and descriptors and screened the reference list of all the available articles. Two groups of keywords linked by the Boolean “OR” operator were included. Covid-19; SARCov2, SARSCoV-2; SARS-CoV-2; COVID; novel coronavirus; coronavirus disease; coronavirus-2019 (first group) and prone positioning; awake prone positioning; self-proning; awake prone position; early awake prone; awake proning (second group). Subsequently, both groups were joined by the Boolean operator AND. Only randomized controlled trials (RCTs) that compared the use of APP with usual care in patient with acute respiratory failure due to COVID-19 were included. No language restrictions were imposed. Two authors screened the studies for eligibility (disagreements were resolved by a third author).</p><p id="par0015" class="elsevierStylePara elsevierViewall">We contacted investigators for unreported data. Cochrane Collaboration tool to assess risk of bias was used. The following variables were evaluated: age, sex, setting, interventions (respiratory support, time session of APP) and outcomes. The primary outcome was intubation rate and secondary outcomes were mortality and oxygenation. We combined the studies through a meta-analysis with dichotomous data as risk ratios (RRs) and continuous data as mean differences (MDs). We assessed the variation in the results by drawing a forest plot and statistical heterogeneity through the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> test at a 95% confidence interval (CI95). According to statistical heterogeneity, fixed-effects model (<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>20%) or a random-effects model (<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>20%) were used. Analyses were performed with Review Manager version 5.4 (The Cochrane Collaboration, Copenhagen, Denmark). The quality of the evidence was assessed according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation criteria guidelines).</p><p id="par0020" class="elsevierStylePara elsevierViewall">Of the 1041 citations, after discarding the duplicates, we identified 59 potentially relevant studies where 51 studies were discarded and eight RCT were included (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> ESM).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–8</span></a> The age of the patients ranged between 49 and 66 years (66.7% male).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Four studies were conducted in the ICU,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3,6</span></a> three in the medical ward<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5,8</span></a> and one study did not report the setting.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The largest study was conducted in six countries: France, USA, Canada, Mexico, Spain, Ireland.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The other studies were carried out in Egypt (one),<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> India (two),<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,7</span></a> Sweden (two)<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> and USA (two).<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,8</span></a> The number of participants ranged from 30<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,4</span></a> to 1121.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> APP time varied between 1 and 16<span class="elsevierStyleHsp" style=""></span>h between the studies, and the supplemental oxygen used (high-flow nasal cannula, nonrebreathing mask, nasal cannula and no invasive ventilation) was variable in both groups.</p><p id="par0030" class="elsevierStylePara elsevierViewall">All studies were at high risk of bias due to performance bias (blinding of patients and staff) and most studies did not detail the orotracheal intubation criteria.</p><p id="par0035" class="elsevierStylePara elsevierViewall">For the meta-analysis, we pooled seven studies because one study did not present outcomes.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> We found significant differences in the intubation rate in favor to the APP group [RR: 0.82 (CI95% 0.71–0.95), <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>: 0%, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>], but no differences in mortality [RR: 0.90 (CI95% 0.73–1.11), <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>: 16%, <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>]. Regarding the intubation rate, we performed sensitivity analysis, excluding the study with the greatest weight<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> [RR: 0.84 (CI95% 0.52–1.35), <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>: 9%, <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> ESM], where we found that the benefit is not maintained.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Five studies, using different assessment of oxygenation (SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,5,8</span></a> SaO<span class="elsevierStyleInf">2</span><a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and ROX index<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a>), describes a positive impact of APP in gas exchange. In turn, two studies (which assessed PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ratio) show a decrease in oxygenation.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> In the remaining study, oxygenation was not evaluate.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Due to the different assessments of oxygenation, no meta-analysis was performed.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The quality of the evidence according to GRADE for the outcomes intubation rate and mortality was ranked as very low. We downgrade for risk of bias (performance bias) and imprecision (due to the number of participants and the wide confidence interval).</p><p id="par0050" class="elsevierStylePara elsevierViewall">This study shows a significant decrease in the intubation rate, without a relevant effect on mortality, in Covid-19 patients supported with APP compare to usual care. It should be noted that the quality of the evidence is low in both results. In addition, our sensitivity analysis (excluding the largest study) showed no benefit.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In addition, the current data do not allow us to draw conclusions regarding the benefit in oxygenation, although most studies show an improvement in oxygenation with APP.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2,5,7,8</span></a>. Only two studies found no improvement in oxygenation,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> where the authors detail it as an unexpected finding, arguing the low adherence to the protocol<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> or the late assessment of oxygenation (48 or 72 post APP)<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> as possible explanations.</p><p id="par0060" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first meta-analysis showing the benefit of APP in interventional studies. Although four previous reviews found significant decrease in the intubation rate and mortality, those results were obtained through meta-analysis of proportions (without a control group), including observational studies and with considerable statistical heterogeneity.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The main limitations of this metanalysis are: (1) the clinical heterogeneity observed with the intervention in terms of session time and oxygenation supplementation; (2) the lack of additional well designed and large scale RCTs to improve the quality of our findings.</p><p id="par0070" class="elsevierStylePara elsevierViewall">APP seems to be a strategy that is useful and relatively easy to implement in Covid-19 patients with acute respiratory failure. The beneficial effect of APP decreasing the intubation rate could be a great help against the potential shortage of mechanical ventilators in some countries in a new pandemic wave.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare not to have any interest conflicts.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0085" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0015" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 783 "Ancho" => 2917 "Tamanyo" => 201136 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Intubation rate. Forest plot of comparisons between APP and UC.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 783 "Ancho" => 2917 "Tamanyo" => 203523 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Mortality. Forest plot of comparisons between APP and UC.</p>" ] ] 2 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 205001 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Ehrmann" 1 => "J. Li" 2 => "M. Ibarra-Estrada" 3 => "Y. Perez" 4 => "I. Pavlov" 5 => "B. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 5 | 7 | 12 |
| 2024 Octubre | 70 | 51 | 121 |
| 2024 Septiembre | 99 | 43 | 142 |
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| 2023 Noviembre | 49 | 34 | 83 |
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| 2023 Septiembre | 51 | 39 | 90 |
| 2023 Agosto | 46 | 13 | 59 |
| 2023 Julio | 71 | 31 | 102 |
| 2023 Junio | 66 | 18 | 84 |
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| 2023 Febrero | 104 | 46 | 150 |
| 2023 Enero | 95 | 52 | 147 |
| 2022 Diciembre | 8 | 2 | 10 |
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