The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis

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A systematic review and metaanalysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "359" "paginaFinal" => "372" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J.A. Mora-Arteaga, O.J. Bernal-Ramírez, S.J. Rodríguez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J.A." "apellidos" => "Mora-Arteaga" "email" => array:1 [ 0 => "javiandrem@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "O.J." "apellidos" => "Bernal-Ramírez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "S.J." 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Una revisión sistemática y metanálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0040" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 4333 "Ancho" => 3251 "Tamanyo" => 1066358 ] ] "descripcion" => array:1 [ "en" => "Ventilation in the prone position and adverse effects. A direct relationship was found between pronation and the risk of pressure ulcers and orotracheal tube obstruction." ] ] ] "textoCompleto" => "IntroductionClinical studies have found that patients with acute respiratory distress syndrome (ARDS) account for approximately 5% of all hospitalized patients subjected to mechanical ventilation.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Most studies have shown that patients with mild ARDS (PaO2/FiO2 200–300) represent only 25% of the cases, while the remaining 75% correspond to patients with moderate or severe ARDS.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> Acute respiratory distress syndrome is associated to an in-hospital mortality rate of approximately 40%.<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a> The mortality rate in turn is conditioned to the severity of the oxygenation defect. In the Berlin definition clinical trial, the mortality rate was found to be 27% in patients with mild ARDS, 32% in cases of moderate ARDS, and 45% in those with severe ARDS.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Although the deterioration of oxygenation is a mortality risk factor in ARDS, patients generally die as a consequence of multiorgan failure, and only a minority (13–19%) die as a result of refractory hypoxemia.<a class="elsevierStyleCrossRefs" href="#bib0015">3,5</a> Although the mortality rate has decreased in the last few decades, probably due to the adoption of protective ventilation strategies (low tidal volume, optimum PEEP level, and limitation of plateau pressure), which lessen ventilator-associated lung injury,<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a> the fatality statistics have remained stable in recent years,<a class="elsevierStyleCrossRefs" href="#bib0010">2,3,5</a> without additional reductions in patients of this kind. It is therefore essential to establish other strategies or treatments that may result in further significant reductions in patient mortality.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>Mechanical ventilation in the prone position has been used for several decades in patients with ARDS with the purpose of improving oxygenation.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> It is currently well recognized that the prone position is associated to important improvements in the oxygenation indices when compared with the supine position. Furthermore, different studies in animals and humans have found that the prone position can reduce ventilator-associated lung injury.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> A number of clinical trials have been made with the aim of extrapolating these results to the clinical setting,<a class="elsevierStyleCrossRefs" href="#bib0050">10–15</a> though none of them have clearly demonstrated a positive impact upon patient survival.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Likewise, the meta-analyses and systematic reviews published to date only suggest a tendency to reduce mortality in patients with severely impaired oxygenation.<a class="elsevierStyleCrossRefs" href="#bib0025">5,9,17–23</a> However, in the time elapsed from the first clinical trial<a class="elsevierStyleCrossRef" href="#bib0050">10</a> to the most recent study,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> there have been important changes in ventilation and pronation strategies, as described in the latest study by Guerin et al.,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> where notorious benefit in terms of survival was documented among patients in the prone position – with an absolute decrease in mortality risk of 37%.In the light of the fact that few strategies have had an impact upon survival in patients with ARDS, it is important that ventilation in the prone position has reappeared with strong results. However, because of the changes in pronation strategy and in the patient inclusion criteria in the most recent studies, we considered it necessary to determine the true impact of pronation, and to define which patients can benefit from it. A meta-analysis was therefore conducted with the primary objective of determining whether ventilation in the prone position reduces mortality in patients with ARDS compared with traditional ventilation in the supine position. As a secondary objective we described the groups of patients that show a positive impact upon survival and the parameters to be applied during the use of this ventilation strategy (timing of the start, daily duration, associated management strategies, etc.). Lastly, based on the results obtained, we aimed to offer a series of evidence-based recommendations on the use of ventilation in the prone position in patients with ARDS.Material and methodsTypes of studiesWe included randomized, controlled clinical trials comparing mechanical ventilation in the prone position versus conventional mechanical ventilation in the supine position in adult patients meeting the Berlin criteria for ARDS.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> We also included patients classified as presenting acute lung injury (ALI)(PaO2/FiO2 200–300mmHg) according to the American–European ARDS consensus Conference of 1994.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>Types of patientsWe included studies that evaluated patients over 16 years of age meeting the diagnostic criteria for ARDS, compared results between ventilation in the prone position versus the supine position, and evaluated mortality.Studies in the pediatric population (under 16 years of age) were excluded, as were studies in animals or which used airway pressure release ventilation (APRV), high-frequency oscillation ventilation (HFOV) or inhaled nitric oxide.Interventions and outcomesThe interventions evaluated were ventilation in the prone position and conventional ventilation in the supine position.The following outcomes were assessed:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Mortality after maximum follow-up</li><li class="elsevierStyleListItem" id="lsti0010">2.Stay in intensive care (days)</li><li class="elsevierStyleListItem" id="lsti0015">3.Days on mechanical ventilation</li><li class="elsevierStyleListItem" id="lsti0020">4.Adverse effects and complications:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">–Ventilator-associated pneumonia (VAP)</li><li class="elsevierStyleListItem" id="lsti0030">–Accidental or non-scheduled extubation</li><li class="elsevierStyleListItem" id="lsti0035">–Tube displacement or selective intubation</li><li class="elsevierStyleListItem" id="lsti0040">–Tube obstruction</li><li class="elsevierStyleListItem" id="lsti0045">–Appearance of pressure ulcers</li><li class="elsevierStyleListItem" id="lsti0050">–Pneumothorax during pronation</li><li class="elsevierStyleListItem" id="lsti0055">–Venous access loss</li></ul></li></ul>The outcomes were stratified by patient subgroups and were predefined taking into account the degree of hypoxemia,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> the use of protective ventilation,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> the duration of ARDS and the daily pronation time.<a class="elsevierStyleCrossRefs" href="#bib0050">10,20,25</a> These factors probably have a decisive influence upon the results of ventilation in the prone position.<a class="elsevierStyleCrossRefs" href="#bib0045">9,17,18,21,22,26–32</a> The subgroups were stratified as follows:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0060">1Severity of ARDS (Berlin classification)<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0065">–Mild (PaO2/FiO2 200–300mmHg)</li><li class="elsevierStyleListItem" id="lsti0070">–Moderate (PaO2/FiO2 100–200mmHg)</li><li class="elsevierStyleListItem" id="lsti0075">–Severe (PaO2/FiO2<100mmHg)</li></ul></li><li class="elsevierStyleListItem" id="lsti0080">2Daily duration of pronation<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0085">–Less than 12h/day</li><li class="elsevierStyleListItem" id="lsti0090">–More than 12h/day</li></ul></li><li class="elsevierStyleListItem" id="lsti0095">3Start of pronation and duration of ARDS</li><li class="elsevierStyleListItem" id="lsti0100">4Tidal volume used<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0105">–Less than 8ml/kg ideal weight</li><li class="elsevierStyleListItem" id="lsti0110">–More than 8ml/kg ideal weight</li></ul></li></ul>Literature search strategyA literature search was made of the PubMed, EMBASE, Cochrane Library and LILACS databases, combining Mesh terms and Keywords: “Prone Position”[Mesh], “Prone Positioning”, “Respiratory Distress Syndrome, Adult”[Mesh], “Acute Respiratory Distress Syndrome”, “ARDS”, “Acute Respiratory Failure”, “Acute Lung Injury”, “Clinical Trial” [Publication Type], “Controlled Clinical Trial” [Publication Type], “Randomized Controlled Trial” [Publication Type], “Clinical Trials as Topic”[Mesh], “Comparative Study” [Publication Type], “Multicenter Study” [Publication Type], “Multicenter Studies as Topic”[Mesh]. The search was limited to the period between 1 January 1974 and 31 December 2013, with no language restrictions.Data extraction and analysisIdentification of trials and data extractionTwo authors (J. Mora and O. Bernal) independently screened the titles and abstracts identified by the search, selecting those studies that met the established inclusion criteria. Information was extracted regarding the study design, randomization procedure, blinding, patient characteristics, inclusion and exclusion criteria, interventions and results. Any disagreements were resolved through examination of the information by a third reviewer (S. Rodriguez).Quality assessmentThe assessment tool recommended by the Cochrane Collaboration<a class="elsevierStyleCrossRef" href="#bib0165">33</a> was used to evaluate the risk of bias that referred to:<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0115">1.Random sequence generation</li><li class="elsevierStyleListItem" id="lsti0120">2.Allocation concealment</li><li class="elsevierStyleListItem" id="lsti0125">3.Blinding of participants and evaluators</li><li class="elsevierStyleListItem" id="lsti0130">4.Incomplete results</li><li class="elsevierStyleListItem" id="lsti0135">5.Selective reporting of results</li><li class="elsevierStyleListItem" id="lsti0140">6.Other sources of bias</li></ul>Statistical analysisThe data from the included studies were qualitatively and quantitatively analyzed per population, intervention and result using the RevMan 5.2 freeware statistical package from the Cochrane Informatics and Knowledge Management Department (<a href="http://tech.cochrane.org/">http://tech.cochrane.org/</a>). The results were quantified and analyzed on an intention-to-treat (ITT) basis; relative heterogeneity was measured with the I2 statistic; and statistical significance was examined using the chi-squared test. Dichotomic results were assessed based on the odds ratio (OR) with the Mantel–Haenszel test and a random effects model. In the case of continuous variables, we calculated the difference in means based on the inverse variance method with a random effects model. Publication bias in turn was assessed by funnel plot analysis, and a sensitivity analysis was made to assess the certainty of the results.The study protocol was not registered.ResultsA total of 371 literature references were identified: PubMed n=134, EMBASE n=160, Cochrane Library n=62 and LILACS n=15. We discarded 124 due to duplication. Twenty-two references were fully reviewed, and of these 7 met the study inclusion criteria (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Characteristics of the studiesThe patient population totaled 2119, of which 1088 were ventilated in the prone position and 1031 in the supine position. The recruitment period of four studies<a class="elsevierStyleCrossRefs" href="#bib0050">10,12,13,15</a> preceded publication of the results of the ARDS network study<a class="elsevierStyleCrossRef" href="#bib0030">6</a> (which demonstrated a decrease in mortality risk in patients ventilated with low tidal volumes). In general, these studies used tidal volumes greater than those currently recommended.The severity of the disease and the mortality risk predicted by the SAPS II were similar in all 7 studies. The four most recent studies only included patients with PaO2/FiO2<200, i.e., with more severely impaired oxygenation.<a class="elsevierStyleCrossRefs" href="#bib0055">11,12,14,16</a> Likewise, the number of hours a day in the prone position was found to increase (from 7–11 to 17–20h/day). The changes in mechanical ventilation protocol were also seen to be related to the time of publication: the three studies that started the recruitment period after publication of the ARDS network study<a class="elsevierStyleCrossRef" href="#bib0030">6</a> used a tidal volume of 6–8ml/kg.<a class="elsevierStyleCrossRefs" href="#bib0055">11,14–16</a> The administered PEEP was generally low. No single protocol for deciding the time of pronation suspension was found. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the general characteristics of the studies.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Bias risk assessmentAll the included studies were randomized, controlled clinical trials. Randomization was carried out on a centralized basis by telephone or sealed and non-transparent envelopes. Given the nature of the intervention subjected to evaluation, it was not possible to blind the patients or the treating medical team–though we consider that this had no effect upon the results. Furthermore, with the exception of a single study,<a class="elsevierStyleCrossRef" href="#bib0065">13</a> the group handling the information of the patients and the results of the analyses was independent and blinded to the treatment groups. No significant losses were reported in the studies, and exclusions after randomization were also few (being mainly due to secondary withdrawal of consent and inclusion error). Three studies ended prematurely. <a class="elsevierStyleCrossRefs" href="#bib0050">10–12</a>We therefore could not obtain an adequate sample for identifying probable differences with optimum statistical power.Prone position and mortalityGlobal mortalityA total of 456 events were recorded in the prone position group (41.9%), versus 483 in the supine position group (46.8%), with an OR of 0.76 (95%CI: 0.54–1.06; p=0.11; I2 63%) showing a tendency in favor of the prone position group–though statistical significance was not reached (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Since the studies had different follow-up periods, and we used the final report on events at the end of this period for the global result, the findings were stratified and evaluated in different time periods: after 28 days (OR: 0.73; 95%CI: 0.41–1.32; p=0.3; I2 85%), after 90 days (OR: 0.64; 95%CI: 0.29–1.40; p=0.26; I2 84%) and after 180 days (OR: 0.97; 95%CI: 0.67–1.40; p=0.26; I2 28%), together with mortality in intensive care (OR: 0.86; 95%CI: 0.61–1.22; p=0.4; I2 31%)–no significant differences being found in each of the groups.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Mortality and protective ventilationOn examining the association between mortality and the administered tidal volume, stratification into two groups was made according to whether a low tidal volume was used as part of a protective ventilation strategy, or a high tidal volume was administered (the latter appearing to be related to the development of ventilator-associated lung injury). Four studies<a class="elsevierStyleCrossRefs" href="#bib0055">11,14–16</a> used a tidal volume 8ml/kg ideal weight, showing a decrease in mortality risk of 36% (OR: 0.58; 95%CI: 0.38–0.87; p=0.009; I2 33%). This finding was not obtained when using a tidal volume >8ml/kg ideal weight (OR: 1.01; 95%CI: 0.77–1.32; p=0.94; I2 18%) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Mortality and number of hours a day in the prone positionAll the studies reported and analyzed data regarding the duration of pronation. In the four most recent publications<a class="elsevierStyleCrossRefs" href="#bib0055">11,12,14,16</a> the number of daily hours was increased (18h on average)–this resulting in a significant decrease in event risk in favor of the group of patients placed in the prone position for more than 12h (OR: 0.6; 95%CI: 0.43–0.83; p=0.002; I2 27%) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>Mortality and start of pronationIn the same way that the number of hours in the prone position appears to be important, so does the timing of the start of patient placement in the prone position. In effect, greater benefit was observed when the patients were placed in the prone position within the first 48h after the start of mechanical ventilation, with an OR of 0.49 (95%CI: 0.35–0.68, p=0.0001; I2 0%) (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Mortality and severity of hypoxemiaThe studies were stratified according to the severity of hypoxemia: moderate (PaO2/FiO2 100–200) or severe (PaO2/FiO2<100). Taccone et al. stratified the population into these two groups; their data were therefore taken separately for analysis. The study published by Voggenreiter et al. reported patients with PaO2/FiO2>200. Five studies<a class="elsevierStyleCrossRefs" href="#bib0050">10–14</a> documented patients with moderate hypoxemia, while two studies<a class="elsevierStyleCrossRefs" href="#bib0070">14,16</a> reported patients with severe hypoxemia. On performing the meta-analysis, the group with severely impaired oxygenation showed clear benefit with the prone position (OR: 0.51; 95%CI: 0.36–1.25; p=0.0001; I2 0%) (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>).<elsevierMultimedia ident="fig0030"></elsevierMultimedia>Prone position, stay in intensive care and days on mechanical ventilationFour studies reported the stay in intensive care,<a class="elsevierStyleCrossRefs" href="#bib0055">11,12,14,16</a> and 5 studies<a class="elsevierStyleCrossRefs" href="#bib0055">11,13–16</a> recorded the days on mechanical ventilation. Analysis was discarded in both cases,<a class="elsevierStyleCrossRef" href="#bib0070">14</a> since different measurement units were used. The study published by Guerin et al.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> reported the results in subgroups of survivors and non-survivors. No differences were found in the results between the two studied groups (stay in intensive care: difference of means −0.05; 95%CI: −2.98–2.89; p=0.00001; I2 95%, and days on mechanical ventilation: difference of means −1.19; 95%CI: −2.74–0.35; p=0.00001; I2 91%) (<a class="elsevierStyleCrossRef" href="#fig0035">Fig. 7</a>).<elsevierMultimedia ident="fig0035"></elsevierMultimedia>Prone position and adverse effectsPressure ulcers were the most frequent adverse events (34%), followed by ventilator-associated pneumonia (21.4%), orotracheal tube obstruction (14.6%), accidental extubation (10.9%), venous access loss (10.9%), pneumothorax (5.8%), and displacement of the orotracheal tube (3.7%).The prone position was associated to a significantly increased risk of orotracheal tube obstruction (OR: 2.19; 95%CI: 1.55–3.09; p<0.0001; I2 0%) and the development of pressure ulcers (OR: 1.53; 95%CI: 1.21–1.94; p=0.0003; I2 0%). No differences were observed in relation to the rest of the described events (<a class="elsevierStyleCrossRef" href="#fig0040">Fig. 8</a>).<elsevierMultimedia ident="fig0040"></elsevierMultimedia>Assessment of publication biasVisual inspection of the funnel plots revealed no evidence of publication bias (<a class="elsevierStyleCrossRef" href="#fig0045">Fig. 9</a>).<elsevierMultimedia ident="fig0045"></elsevierMultimedia>DiscussionThe primary objective of our study was to examine the impact of mechanical ventilation in the prone position upon mortality in patients with ARDS. Global assessment of the results revealed a nonsignificant tendency to reduce mortality risk in favor of the prone position group. However, on individually analyzing the studies, we found that the most recent trials<a class="elsevierStyleCrossRefs" href="#bib0055">11,12,14,16</a> incorporated a number of changes in both the inclusion criteria and in the prone position protocol, based on the analysis of the probable causes underlying the discouraging results recorded in the earlier studies.<a class="elsevierStyleCrossRefs" href="#bib0050">10,13,15</a> A first change was the inclusion of more severely compromised patients, with PaO2/FiO2<200, while a second change was the prolongation of pronation time to over 16 consecutive hours a day. A third change was the utilization of protective ventilation strategies with a tidal volume of <8ml/kg ideal weight, the maintenance of a plateau pressure of <30cmH2O, and titration of the optimum PEEP level according to the recommendations of the ARDS network. On examining the studies linearly over time, we observed a tendency to gradually favor the prone position, culminating in the study published by Guerin et al.,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> where a strong reduction in mortality risk was recorded in favor of pronation (HR 0.44; 95%CI: 0.29–0.67; p=0.001 after 90 days). These findings are consistent with those of two recent meta-analyses. The first study was carried out by Beitler et al.,<a class="elsevierStyleCrossRef" href="#bib0170">34</a> who conducted a meta-analysis of individual patient data, including the PROSEVA study,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> assessing mortality after 60 days, with the identification of a nonsignificant tendency in favor of pronation (RR: 0.83; 95%CI: 0.68–1.02; p=0.073). The second study was published by Lee et al.,<a class="elsevierStyleCrossRef" href="#bib0175">35</a> based on broader inclusion criteria and a larger number of studies, and identified a global decrease in mortality risk, though with a confidence interval very close to one (OR: 0.77; 95%CI: 0.59–0.99; p=0.039).However, interesting data were obtained on stratifying the results by subgroups, supporting our theory regarding the evolution and optimization of the prone position ventilation strategy based on plausible physiology and clear clinical characteristics. Firstly, the utilization of a low tidal volume (<8ml/kg ideal weight) in patients with ARDS became generalized after publication of the ARDS network study<a class="elsevierStyleCrossRef" href="#bib0030">6</a>, which revealed a decrease in mortality risk probably related to the generation of lesser mechanical stress upon the alveolar membrane by preventing overdistension and improving alveolar stability.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> This, being associated to recruitment capacity and homogenization of the distribution of ventilation, flow and airway pressures attributed to pronation,<a class="elsevierStyleCrossRef" href="#bib0185">37</a> probably also produce an additive effect in the prevention and reduction of ventilator-associated lung injury. Thus, on evaluating the subgroup of patients in which a tidal volume of <8ml/kg ideal weight was used,<a class="elsevierStyleCrossRefs" href="#bib0055">11,14–16</a> a significant decrease in mortality risk was noted in comparison with the group receiving a greater tidal volume<a class="elsevierStyleCrossRefs" href="#bib0050">10,13,15</a>–these findings possibly being attributable to the decrease in ventilator-associated lung injury. Beitler et al.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> and Lee et al.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> also recorded a significant decrease in mortality risk in those studies that used low tidal volumes (RR: 0.66; 95%CI: 0.5–0.86; p=0.002 and OR: 0.62; 95%CI: 0.48–0.69; p=0.015, respectively). Beitler et al.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> in turn performed a metaregression analysis that revealed a dose–response relationship between the mean basal tidal volume and the relative risk of death after 60 days during pronation. Specifically, a decrease in mean basal tidal volume of 1ml/kg ideal weight was seen to be associated to a 16.7% mortality risk.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>The degree of alveolar recruitment in the prone position also requires consideration. Acute respiratory distress syndrome is characterized by disruption of the alveolar-capillary barrier, with increased permeability of the latter and the production of flooding and alveolar edema furthermore associated to the depletion of surfactant–thus giving rise to alveolar instability and collapse.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> Pulmonary involvement is heterogeneous, with well aerated lung regions that participate in gas exchange, and other regions that have collapsed as a result of the overpressure exerted by the interstitial edema and alveolar flooding<a class="elsevierStyleCrossRefs" href="#bib0195">39,40</a>–these mechanisms explaining the decrease in lung volume in these patients.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> Pronation makes it possible to recruit these affected zones,<a class="elsevierStyleCrossRef" href="#bib0185">37</a> redistributing and homogenizing ventilation,<a class="elsevierStyleCrossRef" href="#bib0150">30</a> reducing the intrapulmonary shunt effect and improving oxygenation, ventilation and lung mechanics.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> However, the degree of recruitment depends on factors such as the severity of lung involvement,<a class="elsevierStyleCrossRef" href="#bib0125">25</a> the pronation time<a class="elsevierStyleCrossRef" href="#bib0195">39</a> and the time elapsed from lung injury to patient placement in the prone position.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>Although the prone position can effectively increase oxygenation when used several days after onset of the disease,<a class="elsevierStyleCrossRef" href="#bib0050">10</a> its application during the early stages was found to offer betters results. During these early stages, all the conditions favoring the effectiveness of pronation are present, such as alveolar edema, reversible collapse and the absence of pulmonary structural alterations.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> In these stages, the reduction in ventilator-associated lung injury risk probably exceeds that obtained when pronation is used in later stages of ARDS, when the damage has already been caused.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> This has been clearly demonstrated in our study, where the patients placed in the prone position within the first 48h of the evolution of the disease showed a clear protective effect referred to mortality risk.In clinical practice, the severity of ARDS has been rated according to the PaO2/FiO2 ratio,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> though in disorders as complex as this syndrome, the PaO2/FiO2 ratio depends on the PEEP level and FiO2 administered, as well as on the prescribed treatments and/or interventions, the comorbidities, and the innate compensatory mechanisms of the disease.<a class="elsevierStyleCrossRef" href="#bib0215">43</a> Despite the presence of these variables, the results obtained allow us to clearly establish that the prone position is indicated in patients with severely impaired oxygenation, as has already been demonstrated in other studies.<a class="elsevierStyleCrossRefs" href="#bib0025">5,17–19,21–23</a> Furthermore, prolongation of the prone position to over 12 consecutive hours a day (18h on average) in patients with severe ARDS is a highly recommended strategy.<a class="elsevierStyleCrossRefs" href="#bib0055">11,12,14,16</a> It is important to note that in patients with mild ARDS, pronation has not been found to offer clinical advantages and is therefore not advised.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In cases of moderate ARDS, the clinical recommendation is likewise not clear, though the results of the post hoc analysis of a meta-analysis<a class="elsevierStyleCrossRef" href="#bib0045">9</a> revealed a certain tendency to benefit patients with PaO2/FiO2<140. Consequently, when taken in combination with the results of the PROSEVA study,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> these data allow us to consider the use of this strategy in this patient subgroup.<a class="elsevierStyleCrossRefs" href="#bib0185">37,44</a>Adverse eventsIn general, ventilation in the prone position is safe, and its complications are infrequent. The most common adverse effects are pressure ulcers and orotracheal tube obstruction. Accidental extubation, displacement of the orotracheal tube, the risk of pneumothorax, and venous access loss exhibited a similar distribution between the two groups. The development of ventilator-associated pneumonia (VAP) was not related to pronation, and its frequency was similar to that reported in previous reviews.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> Although the incidence of adverse events is low, we think that it is largely conditioned by treating team experience with the prone position, and the existence of guides and protocols with the indications, contraindications and safety measures to be adopted during the procedure.ConclusionsThe prone position offers clinical benefits such as improved oxygenation, by optimizing lung recruitment and the ventilation–perfusion ratio, and probably also prevents and reduces ventilator-associated lung injury by homogenizing the stress and strain upon the lung parenchyma, resulting in a decrease in mortality risk.Based on the results obtained, the prone position can be recommended in patients with severe hypoxemia (PaO2/FiO2<100), associated to a low tidal volume (<8ml/kg ideal weight), during a period of over 16h a day, and starting early during the course of the disease (<48h). These consequently would be the indications and associated strategies to be included in pronation protocols.Pronation requires no special equipment, but should be carried out by trained personnel and adopting the required safety measures in order to avoid associated complications.Financial supportThe authors declare that no financial support has been received for this study from any government or private organism.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres557888" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methodology" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec573316" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres557889" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Metodología" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec573315" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Types of studies" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Types of patients" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Interventions and outcomes" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Literature search strategy" ] 4 => array:3 [ "identificador" => "sec0035" "titulo" => "Data extraction and analysis" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Identification of trials and data extraction" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Quality assessment" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Statistical analysis" ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0055" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Characteristics of the studies" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Bias risk assessment" ] 2 => array:3 [ "identificador" => "sec0070" "titulo" => "Prone position and mortality" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Global mortality" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Mortality and protective ventilation" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Mortality and number of hours a day in the prone position" ] 3 => array:2 [ "identificador" => "sec0090" "titulo" => "Mortality and start of pronation" ] 4 => array:2 [ "identificador" => "sec0095" "titulo" => "Mortality and severity of hypoxemia" ] 5 => array:2 [ "identificador" => "sec0100" "titulo" => "Prone position, stay in intensive care and days on mechanical ventilation" ] 6 => array:2 [ "identificador" => "sec0105" "titulo" => "Prone position and adverse effects" ] 7 => array:2 [ "identificador" => "sec0110" "titulo" => "Assessment of publication bias" ] ] ] ] ] 7 => array:3 [ "identificador" => "sec0115" "titulo" => "Discussion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0120" "titulo" => "Adverse events" ] ] ] 8 => array:2 [ "identificador" => "sec0125" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0130" "titulo" => "Financial support" ] 10 => array:2 [ "identificador" => "sec0135" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-09-12" "fechaAceptado" => "2014-11-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec573316" "palabras" => array:3 [ 0 => "Respiratory distress syndrome, adult" 1 => "Prone position" 2 => "Meta-analysis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec573315" "palabras" => array:3 [ 0 => "Síndrome de dificultad respiratoria del adulto" 1 => "Posición prona" 2 => "Metanálisis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionProne position ventilation has been shown to improve oxygenation and ventilatory mechanics in patients with acute respiratory distress syndrome. We evaluated whether prone ventilation reduces the risk of mortality in adult patients with acute respiratory distress syndrome versus supine ventilation. MethodologyA meta-analysis of randomized controlled trials comparing patients in supine versus prone position was performed. A search was conducted of the Pubmed, Embase, Cochrane Library, and LILACS databases. Mortality, hospital length of stay, days of mechanical ventilation and adverse effects were evaluated. ResultsSeven randomized controlled trials (2119 patients) were included in the analysis. The prone position showed a nonsignificant tendency to reduce mortality (OR: 0.76; 95%CI: 0.54–1.06; p=0.11, I2 63%). When stratified by subgroups, a significant decrease was seen in the risk of mortality in patients ventilated with low tidal volume (OR: 0.58; 95%CI: 0.38–0.87; p=0.009, I2 33%), prolonged pronation (OR: 0.6; 95%CI: 0.43–0.83; p=0.002, I2 27%), start within the first 48h of disease evolution (OR 0.49; 95%CI 0.35–0.68; p=0.0001, I2 0%) and severe hypoxemia (OR: 0.51: 95%CI: 0.36–1.25; p=0.0001, I2 0%). Adverse effects associated with pronation were the development of pressure ulcers and endotracheal tube obstruction. ConclusionsProne position ventilation is a safe strategy and reduces mortality in patients with severely impaired oxygenation. It should be started early, for prolonged periods, and should be associated to a protective ventilation strategy." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methodology" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa ventilación en posición prona ha demostrado mejorar la oxigenación y la mecánica pulmonar en pacientes con síndrome de dificultad respiratoria aguda. Nosotros evaluamos si la posición prona disminuye el riesgo de mortalidad en pacientes adultos con síndrome de dificultad respiratoria aguda versus ventilación en posición supina. MetodologíaSe realizó un metanálisis de ensayos clínicos controlados aleatorizados que compararon pacientes en posición prona versus supina. Se realizó una búsqueda en Pubmed, Embase, Cochrane Library y LILACS. Se evaluó mortalidad, estancia hospitalaria, días de ventilación mecánica y efectos adversos. ResultadosSiete ensayos clínicos controlados aleatorizados (2.119 pacientes) fueron incluidos en el análisis. La posición prona mostró una tendencia no significativa a disminuir la mortalidad (OR: 0,76; IC 95%: 0,54–1,06; p=0,11; I2 63%). Al estratificar por subgrupos se encontró una disminución significativa en el riesgo de mortalidad en los pacientes ventilados con volumen corriente bajo (OR: 0,58; IC 95%: 0,38–0,87; p=0,009; I2 33%), pronación prolongada (OR: 0,6; IC 95%: 0,43–0,83; p=0,002; I2 27%), instauración antes de 48h de evolución de la enfermedad (OR: 0,49; IC 95%: 0,35–0,68; p=0,0001; I2 0%) e hipoxemia severa (OR: 0,51; IC 95%: 0,36–1,25; p=0,0001; I2 0%). Los efectos adversos relacionados con la pronación fueron el desarrollo de úlceras por presión y obstrucción del tubo orotraqueal. ConclusionesLa ventilación en posición prona es una estrategia segura y disminuye la mortalidad en los pacientes con compromiso severo de la oxigenación, debe ser instaurada tempranamente, durante periodos prolongados y asociada a una estrategia de ventilación protectora." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Metodología" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Mora-Arteaga JA, Bernal-Ramírez OJ, Rodríguez SJ. Efecto de la ventilación mecánica en posición prona en pacientes con síndrome de dificultad respiratoria aguda. Una revisión sistemática y metanálisis. Med Intensiva. 2015;39:359–372." ] ] "multimedia" => array:10 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1830 "Ancho" => 2424 "Tamanyo" => 269652 ] ] "descripcion" => array:1 [ "en" => "Study screening process. ON: nitric oxide." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1439 "Ancho" => 3250 "Tamanyo" => 403561 ] ] "descripcion" => array:1 [ "en" => "Global mortality and bias risk. Mortality was evaluated up until the end of follow-up in each study. The bias risk of each study was scored as high (−), intermediate (?) or low (+)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1404 "Ancho" => 3251 "Tamanyo" => 336249 ] ] "descripcion" => array:1 [ "en" => "Mortality and protective ventilation. The prone position exerted a protective effect in patients ventilated with a tidal volume <8ml/kg ideal weight." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1406 "Ancho" => 3251 "Tamanyo" => 343349 ] ] "descripcion" => array:1 [ "en" => "Mortality and hours a day in the prone position. Significant differences were found in favor of the group placed in the prone position during more than 12h a day." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1352 "Ancho" => 3251 "Tamanyo" => 332590 ] ] "descripcion" => array:1 [ "en" => "Mortality and timing of the start of pronation. Pronation within the first 48h was associated to a decrease in mortality risk." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1595 "Ancho" => 3251 "Tamanyo" => 385207 ] ] "descripcion" => array:1 [ "en" => "Mortality and severity of hypoxemia. Taccone et al. stratified the patients into individuals with moderate or severe hypoxemia. The data of each group were taken separately to the effects of analysis." ] ] 6 => array:7 [ "identificador" => "fig0035" "etiqueta" => "Figure 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 1600 "Ancho" => 3251 "Tamanyo" => 429337 ] ] "descripcion" => array:1 [ "en" => "Ventilation in the prone position, stay in intensive care and days on mechanical ventilation. No significant differences were found between the groups of patients." ] ] 7 => array:7 [ "identificador" => "fig0040" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 4333 "Ancho" => 3251 "Tamanyo" => 1066358 ] ] "descripcion" => array:1 [ "en" => "Ventilation in the prone position and adverse effects. A direct relationship was found between pronation and the risk of pressure ulcers and orotracheal tube obstruction." ] ] 8 => array:7 [ "identificador" => "fig0045" "etiqueta" => "Figure 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 1663 "Ancho" => 2301 "Tamanyo" => 66206 ] ] "descripcion" => array:1 [ "en" => "Funnel plot. Visual inspection reveals no selection bias." ] ] 9 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "NR: not reported; PAOP: pulmonary artery occlusion pressure; PaO2/FiO2: ratio between partial pressure of oxygen in arterial blood and fraction of inspired oxygen; PEEP: positive end-expiratory pressure; TV: tidal volume." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study/characteristics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gatinoni et al. (2001) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Guerin et al.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Voggenreiter et al.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mancebo et al.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fernandez et al.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Taccone et al.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Guérin et al.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total patients (no.) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">304 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">791 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">136 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">342 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">466 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Recruitment period \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">December 1996–October 1999 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">December 1998–december 2002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">September 1999–September 2001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">December 1998–September 2002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">September 2003–September 2004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">February 2004–October 2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">January 2008–July 2011 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Follow-up period \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">180 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Until hospital discharge \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">180 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Inclusion criteria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2≤200 with PEEP≥5cmH2O, PaO2/FiO2≤300 with PEEP≥10cmH2O, PAOP≤18mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2≤300 expected mechanical ventilation time >48h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2≤200 with PEEP≥5cmH2O, PaO2/FiO2≤300 with PEEP≥5cmH2O, PAOP≤18mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2≤200 with PEEP≥5cmH2O, PAOP≤18mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2≤200 with PEEP≥5cmH2O, PAOP≤18mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2≤200 with PEEP≥5cmH2O, PAOP≤18mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2≤150 with PEEP≥5cmH2O, TV 6ml/kg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top">Severity (mean)</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">127.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">152.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">221.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">146.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">155.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">113 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">APACHE II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SAPS II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SOFA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top">Ventilator settings</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PEEP (cmH2O) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tidal volume (ml/kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top">Prone position</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Time before pronation (hours) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hours a day in pronation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total days in pronation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Pronation suspension criterion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Completion of 10 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Improvement of PaO2/FiO2>30% with FiO2<60% and PEEP<8 cmH2O; no sepsis or resolution of cause of ventilation failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2>300 during >48h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Start of weaning from ventilator \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2>250 with PEEP<8cmH2O during >12h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Resolution of ventilation failure and/or 28 days from admission to study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PaO2/FiO2>150 PEEP<10cmH2O and FiO2<0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="8" align="left" valign="top">Methodology</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Allocation concealment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, centralized randomization by telephone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, randomization by sealed and non-transparent envelopes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, centralized randomization by telephone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, centralized randomization by call center \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, centralized randomization by telephone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, centralized randomization by web-based system \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Exclusions after randomization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, one patient in each group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 7 patients in supine group and 4 in prone position group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 2 patients in supine group and 4 in prone position group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, one patient in each group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 5 patients in supine group and 3 in prone position group \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Losses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, one patient in each group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 2 patients in prone position group and one in supine group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, one patient in each group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, two patients in each group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Supine to prone cross-over \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 12 patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 81 patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 5 patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 2 patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes, 20 patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Early termination \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab899579.png" ] 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The effects of prone position ventilation in patients with acute respiratory distress syndrome. A systematic review and metaanalysis

Efecto de la ventilación mecánica en posición prona en pacientes con síndrome de dificultad respiratoria aguda. Una revisión sistemática y metanálisis

J.A. Mora-Arteagaa,

Corresponding author

javiandrem@yahoo.com

Corresponding author.

, O.J. Bernal-Ramírezb, S.J. Rodríguezc

a Medicina Crítica y Cuidado Intensivo, Universidad del Rosario, Fundación Santa Fe de Bogotá-Hospital Universitario, Bogotá D.C., Colombia

b Medicina Crítica y Cuidado Intensivo, Clínica Nueva-Hospital de Suba, Bogotá D.C., Colombia

c Medicina Crítica y Cuidado Intensivo, Clínica Nueva-Hospital Universitario la Samaritana, Bogotá D.C., Colombia

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in-hospital mortality rate of approximately 40&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> The mortality rate in turn is conditioned to the severity of the oxygenation defect&#46; In the Berlin definition clinical trial&#44; the mortality rate was found to be 27&#37; in patients with mild ARDS&#44; 32&#37; in cases of moderate ARDS&#44; and 45&#37; in those with severe ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Although the deterioration of oxygenation is a mortality risk factor in ARDS&#44; patients generally die as a consequence of multiorgan failure&#44; and only a minority &#40;13&#8211;19&#37;&#41; die as a result of refractory hypoxemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a> Although the mortality rate has decreased in the last few decades&#44; probably due to the adoption of protective ventilation strategies &#40;low tidal volume&#44; optimum PEEP level&#44; and limitation of plateau pressure&#41;&#44; which lessen ventilator-associated lung injury&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> the fatality statistics have remained stable in recent years&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;5</span></a> without additional reductions in patients of this kind&#46; It is therefore essential to establish other strategies or treatments that may result in further significant reductions in patient mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Mechanical ventilation in the prone position has been used for several decades in patients with ARDS with the purpose of improving oxygenation&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> It is currently well recognized that the prone position is associated to important improvements in the oxygenation indices when compared with the supine position&#46; Furthermore&#44; different studies in animals and humans have found that the prone position can reduce ventilator-associated lung injury&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A number of clinical trials have been made with the aim of extrapolating these results to the clinical setting&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;15</span></a> though none of them have clearly demonstrated a positive impact upon patient survival&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Likewise&#44; the meta-analyses and systematic reviews published to date only suggest a tendency to reduce mortality in patients with severely impaired oxygenation&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;9&#44;17&#8211;23</span></a> However&#44; in the time elapsed from the first clinical trial<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> to the most recent study&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> there have been important changes in ventilation and pronation strategies&#44; as described in the latest study by Guerin et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> where notorious benefit in terms of survival was documented among patients in the prone position &#8211; with an absolute decrease in mortality risk of 37&#37;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In the light of the fact that few strategies have had an impact upon survival in patients with ARDS&#44; it is important that ventilation in the prone position has reappeared with strong results&#46; However&#44; because of the changes in pronation strategy and in the patient inclusion criteria in the most recent studies&#44; we considered it necessary to determine the true impact of pronation&#44; and to define which patients can benefit from it&#46; A meta-analysis was therefore conducted with the primary objective of determining whether ventilation in the prone position reduces mortality in patients with ARDS compared with traditional ventilation in the supine position&#46; As a secondary objective we described the groups of patients that show a positive impact upon survival and the parameters to be applied during the use of this ventilation strategy &#40;timing of the start&#44; daily duration&#44; associated management strategies&#44; etc&#46;&#41;&#46; Lastly&#44; based on the results obtained&#44; we aimed to offer a series of evidence-based recommendations on the use of ventilation in the prone position in patients with ARDS&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Types of studies</span><p id="par0020" class="elsevierStylePara elsevierViewall">We included randomized&#44; controlled clinical trials comparing mechanical ventilation in the prone position versus conventional mechanical ventilation in the supine position in adult patients meeting the Berlin criteria for ARDS&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> We also included patients classified as presenting acute lung injury &#40;ALI&#41;&#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> 200&#8211;300<span class="elsevierStyleHsp" style=""></span>mmHg&#41; according to the American&#8211;European ARDS consensus Conference of 1994&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Types of patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">We included studies that evaluated patients over 16 years of age meeting the diagnostic criteria for ARDS&#44; compared results between ventilation in the prone position versus the supine position&#44; and evaluated mortality&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Studies in the pediatric population &#40;under 16 years of age&#41; were excluded&#44; as were studies in animals or which used airway pressure release ventilation &#40;APRV&#41;&#44; high-frequency oscillation ventilation &#40;HFOV&#41; or inhaled nitric oxide&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Interventions and outcomes</span><p id="par0035" class="elsevierStylePara elsevierViewall">The interventions evaluated were ventilation in the prone position and conventional ventilation in the supine position&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The following outcomes were assessed&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Mortality after maximum follow-up</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Stay in intensive care &#40;days&#41;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Days on mechanical ventilation</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Adverse effects and complications&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8211;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Ventilator-associated pneumonia &#40;VAP&#41;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8211;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Accidental or non-scheduled extubation</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8211;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Tube displacement or selective intubation</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8211;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Tube obstruction</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8211;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Appearance of pressure ulcers</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8211;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Pneumothorax during pronation</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8211;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Venous access loss</p></li></ul></p></li></ul></p><p id="par0100" class="elsevierStylePara elsevierViewall">The outcomes were stratified by patient subgroups and were predefined taking into account the degree of hypoxemia&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> the use of protective ventilation&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> the duration of ARDS and the daily pronation time&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;20&#44;25</span></a> These factors probably have a decisive influence upon the results of ventilation in the prone position&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;17&#44;18&#44;21&#44;22&#44;26&#8211;32</span></a> The subgroups were stratified as follows&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">1</span><p id="par0105" class="elsevierStylePara elsevierViewall">Severity of ARDS &#40;Berlin classification&#41;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8211;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Mild &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> 200&#8211;300<span class="elsevierStyleHsp" style=""></span>mmHg&#41;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8211;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Moderate &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> 100&#8211;200<span class="elsevierStyleHsp" style=""></span>mmHg&#41;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8211;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Severe &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mmHg&#41;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">2</span><p id="par0125" class="elsevierStylePara elsevierViewall">Daily duration of pronation<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8211;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Less than 12<span class="elsevierStyleHsp" style=""></span>h&#47;day</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8211;</span><p id="par0135" class="elsevierStylePara elsevierViewall">More than 12<span class="elsevierStyleHsp" style=""></span>h&#47;day</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">3</span><p id="par0140" class="elsevierStylePara elsevierViewall">Start of pronation and duration of ARDS</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">4</span><p id="par0145" class="elsevierStylePara elsevierViewall">Tidal volume used<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8211;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Less than 8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8211;</span><p id="par0155" class="elsevierStylePara elsevierViewall">More than 8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight</p></li></ul></p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Literature search strategy</span><p id="par0160" class="elsevierStylePara elsevierViewall">A literature search was made of the PubMed&#44; EMBASE&#44; Cochrane Library and LILACS databases&#44; combining Mesh terms and Keywords&#58; &#8220;Prone Position&#8221;&#91;Mesh&#93;&#44; &#8220;Prone Positioning&#8221;&#44; &#8220;Respiratory Distress Syndrome&#44; Adult&#8221;&#91;Mesh&#93;&#44; &#8220;Acute Respiratory Distress Syndrome&#8221;&#44; &#8220;ARDS&#8221;&#44; &#8220;Acute Respiratory Failure&#8221;&#44; &#8220;Acute Lung Injury&#8221;&#44; &#8220;Clinical Trial&#8221; &#91;Publication Type&#93;&#44; &#8220;Controlled Clinical Trial&#8221; &#91;Publication Type&#93;&#44; &#8220;Randomized Controlled Trial&#8221; &#91;Publication Type&#93;&#44; &#8220;Clinical Trials as Topic&#8221;&#91;Mesh&#93;&#44; &#8220;Comparative Study&#8221; &#91;Publication Type&#93;&#44; &#8220;Multicenter Study&#8221; &#91;Publication Type&#93;&#44; &#8220;Multicenter Studies as Topic&#8221;&#91;Mesh&#93;&#46; The search was limited to the period between 1 January 1974 and 31 December 2013&#44; with no language restrictions&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Data extraction and analysis</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Identification of trials and data extraction</span><p id="par0165" class="elsevierStylePara elsevierViewall">Two authors &#40;J&#46; Mora and O&#46; Bernal&#41; independently screened the titles and abstracts identified by the search&#44; selecting those studies that met the established inclusion criteria&#46; Information was extracted regarding the study design&#44; randomization procedure&#44; blinding&#44; patient characteristics&#44; inclusion and exclusion criteria&#44; interventions and results&#46; Any disagreements were resolved through examination of the information by a third reviewer &#40;S&#46; Rodriguez&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Quality assessment</span><p id="par0170" class="elsevierStylePara elsevierViewall">The assessment tool recommended by the Cochrane Collaboration<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> was used to evaluate the risk of bias that referred to&#58;<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">1&#46;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Random sequence generation</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">2&#46;</span><p id="par0180" class="elsevierStylePara elsevierViewall">Allocation concealment</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">3&#46;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Blinding of participants and evaluators</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">4&#46;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Incomplete results</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">5&#46;</span><p id="par0195" class="elsevierStylePara elsevierViewall">Selective reporting of results</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">6&#46;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Other sources of bias</p></li></ul></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Statistical analysis</span><p id="par0205" class="elsevierStylePara elsevierViewall">The data from the included studies were qualitatively and quantitatively analyzed per population&#44; intervention and result using the RevMan 5&#46;2 freeware statistical package from the Cochrane Informatics and Knowledge Management Department &#40;<a href="http://tech.cochrane.org/">http&#58;&#47;&#47;tech&#46;cochrane&#46;org&#47;</a>&#41;&#46; The results were quantified and analyzed on an intention-to-treat &#40;ITT&#41; basis&#59; relative heterogeneity was measured with the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> statistic&#59; and statistical significance was examined using the chi-squared test&#46; Dichotomic results were assessed based on the odds ratio &#40;OR&#41; with the Mantel&#8211;Haenszel test and a random effects model&#46; In the case of continuous variables&#44; we calculated the difference in means based on the inverse variance method with a random effects model&#46; Publication bias in turn was assessed by funnel plot analysis&#44; and a sensitivity analysis was made to assess the certainty of the results&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The study protocol was not registered&#46;</p></span></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><p id="par0215" class="elsevierStylePara elsevierViewall">A total of 371 literature references were identified&#58; PubMed n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>134&#44; EMBASE n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>160&#44; Cochrane Library n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>62 and LILACS n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#46; We discarded 124 due to duplication&#46; Twenty-two references were fully reviewed&#44; and of these 7 met the study inclusion criteria &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Characteristics of the studies</span><p id="par0220" class="elsevierStylePara elsevierViewall">The patient population totaled 2119&#44; of which 1088 were ventilated in the prone position and 1031 in the supine position&#46; The recruitment period of four studies<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;12&#44;13&#44;15</span></a> preceded publication of the results of the ARDS network study<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> &#40;which demonstrated a decrease in mortality risk in patients ventilated with low tidal volumes&#41;&#46; In general&#44; these studies used tidal volumes greater than those currently recommended&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The severity of the disease and the mortality risk predicted by the SAPS <span class="elsevierStyleSmallCaps">II</span> were similar in all 7 studies&#46; The four most recent studies only included patients with PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>200&#44; i&#46;e&#46;&#44; with more severely impaired oxygenation&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12&#44;14&#44;16</span></a> Likewise&#44; the number of hours a day in the prone position was found to increase &#40;from 7&#8211;11 to 17&#8211;20<span class="elsevierStyleHsp" style=""></span>h&#47;day&#41;&#46; The changes in mechanical ventilation protocol were also seen to be related to the time of publication&#58; the three studies that started the recruitment period after publication of the ARDS network study<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> used a tidal volume of 6&#8211;8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;14&#8211;16</span></a> The administered PEEP was generally low&#46; No single protocol for deciding the time of pronation suspension was found&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the general characteristics of the studies&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Bias risk assessment</span><p id="par0230" class="elsevierStylePara elsevierViewall">All the included studies were randomized&#44; controlled clinical trials&#46; Randomization was carried out on a centralized basis by telephone or sealed and non-transparent envelopes&#46; Given the nature of the intervention subjected to evaluation&#44; it was not possible to blind the patients or the treating medical team&#8211;though we consider that this had no effect upon the results&#46; Furthermore&#44; with the exception of a single study&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> the group handling the information of the patients and the results of the analyses was independent and blinded to the treatment groups&#46; No significant losses were reported in the studies&#44; and exclusions after randomization were also few &#40;being mainly due to secondary withdrawal of consent and inclusion error&#41;&#46; Three studies ended prematurely&#46; <a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a>We therefore could not obtain an adequate sample for identifying probable differences with optimum statistical power&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Prone position and mortality</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Global mortality</span><p id="par0235" class="elsevierStylePara elsevierViewall">A total of 456 events were recorded in the prone position group &#40;41&#46;9&#37;&#41;&#44; versus 483 in the supine position group &#40;46&#46;8&#37;&#41;&#44; with an OR of 0&#46;76 &#40;95&#37;CI&#58; 0&#46;54&#8211;1&#46;06&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;11&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 63&#37;&#41; showing a tendency in favor of the prone position group&#8211;though statistical significance was not reached &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Since the studies had different follow-up periods&#44; and we used the final report on events at the end of this period for the global result&#44; the findings were stratified and evaluated in different time periods&#58; after 28 days &#40;OR&#58; 0&#46;73&#59; 95&#37;CI&#58; 0&#46;41&#8211;1&#46;32&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 85&#37;&#41;&#44; after 90 days &#40;OR&#58; 0&#46;64&#59; 95&#37;CI&#58; 0&#46;29&#8211;1&#46;40&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;26&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 84&#37;&#41; and after 180 days &#40;OR&#58; 0&#46;97&#59; 95&#37;CI&#58; 0&#46;67&#8211;1&#46;40&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;26&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 28&#37;&#41;&#44; together with mortality in intensive care &#40;OR&#58; 0&#46;86&#59; 95&#37;CI&#58; 0&#46;61&#8211;1&#46;22&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;4&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 31&#37;&#41;&#8211;no significant differences being found in each of the groups&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Mortality and protective ventilation</span><p id="par0240" class="elsevierStylePara elsevierViewall">On examining the association between mortality and the administered tidal volume&#44; stratification into two groups was made according to whether a low tidal volume was used as part of a protective ventilation strategy&#44; or a high tidal volume was administered &#40;the latter appearing to be related to the development of ventilator-associated lung injury&#41;&#46; Four studies<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;14&#8211;16</span></a> used a tidal volume 8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight&#44; showing a decrease in mortality risk of 36&#37; &#40;OR&#58; 0&#46;58&#59; 95&#37;CI&#58; 0&#46;38&#8211;0&#46;87&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 33&#37;&#41;&#46; This finding was not obtained when using a tidal volume &#62;8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight &#40;OR&#58; 1&#46;01&#59; 95&#37;CI&#58; 0&#46;77&#8211;1&#46;32&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;94&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 18&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Mortality and number of hours a day in the prone position</span><p id="par0245" class="elsevierStylePara elsevierViewall">All the studies reported and analyzed data regarding the duration of pronation&#46; In the four most recent publications<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12&#44;14&#44;16</span></a> the number of daily hours was increased &#40;18<span class="elsevierStyleHsp" style=""></span>h on average&#41;&#8211;this resulting in a significant decrease in event risk in favor of the group of patients placed in the prone position for more than 12<span class="elsevierStyleHsp" style=""></span>h &#40;OR&#58; 0&#46;6&#59; 95&#37;CI&#58; 0&#46;43&#8211;0&#46;83&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 27&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Mortality and start of pronation</span><p id="par0250" class="elsevierStylePara elsevierViewall">In the same way that the number of hours in the prone position appears to be important&#44; so does the timing of the start of patient placement in the prone position&#46; In effect&#44; greater benefit was observed when the patients were placed in the prone position within the first 48<span class="elsevierStyleHsp" style=""></span>h after the start of mechanical ventilation&#44; with an OR of 0&#46;49 &#40;95&#37;CI&#58; 0&#46;35&#8211;0&#46;68&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Mortality and severity of hypoxemia</span><p id="par0255" class="elsevierStylePara elsevierViewall">The studies were stratified according to the severity of hypoxemia&#58; moderate &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> 100&#8211;200&#41; or severe &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>100&#41;&#46; Taccone et al&#46; stratified the population into these two groups&#59; their data were therefore taken separately for analysis&#46; The study published by Voggenreiter et al&#46; reported patients with PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>200&#46; Five studies<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;14</span></a> documented patients with moderate hypoxemia&#44; while two studies<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;16</span></a> reported patients with severe hypoxemia&#46; On performing the meta-analysis&#44; the group with severely impaired oxygenation showed clear benefit with the prone position &#40;OR&#58; 0&#46;51&#59; 95&#37;CI&#58; 0&#46;36&#8211;1&#46;25&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Prone position&#44; stay in intensive care and days on mechanical ventilation</span><p id="par0260" class="elsevierStylePara elsevierViewall">Four studies reported the stay in intensive care&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12&#44;14&#44;16</span></a> and 5 studies<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;13&#8211;16</span></a> recorded the days on mechanical ventilation&#46; Analysis was discarded in both cases&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> since different measurement units were used&#46; The study published by Guerin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> reported the results in subgroups of survivors and non-survivors&#46; No differences were found in the results between the two studied groups &#40;stay in intensive care&#58; difference of means &#8722;0&#46;05&#59; 95&#37;CI&#58; &#8722;2&#46;98&#8211;2&#46;89&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 95&#37;&#44; and days on mechanical ventilation&#58; difference of means &#8722;1&#46;19&#59; 95&#37;CI&#58; &#8722;2&#46;74&#8211;0&#46;35&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 91&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#41;&#46;</p><elsevierMultimedia ident="fig0035"></elsevierMultimedia></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Prone position and adverse effects</span><p id="par0265" class="elsevierStylePara elsevierViewall">Pressure ulcers were the most frequent adverse events &#40;34&#37;&#41;&#44; followed by ventilator-associated pneumonia &#40;21&#46;4&#37;&#41;&#44; orotracheal tube obstruction &#40;14&#46;6&#37;&#41;&#44; accidental extubation &#40;10&#46;9&#37;&#41;&#44; venous access loss &#40;10&#46;9&#37;&#41;&#44; pneumothorax &#40;5&#46;8&#37;&#41;&#44; and displacement of the orotracheal tube &#40;3&#46;7&#37;&#41;&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The prone position was associated to a significantly increased risk of orotracheal tube obstruction &#40;OR&#58; 2&#46;19&#59; 95&#37;CI&#58; 1&#46;55&#8211;3&#46;09&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41; and the development of pressure ulcers &#40;OR&#58; 1&#46;53&#59; 95&#37;CI&#58; 1&#46;21&#8211;1&#46;94&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0003&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41;&#46; No differences were observed in relation to the rest of the described events &#40;<a class="elsevierStyleCrossRef" href="#fig0040">Fig&#46; 8</a>&#41;&#46;</p><elsevierMultimedia ident="fig0040"></elsevierMultimedia></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Assessment of publication bias</span><p id="par0275" class="elsevierStylePara elsevierViewall">Visual inspection of the funnel plots revealed no evidence of publication bias &#40;<a class="elsevierStyleCrossRef" href="#fig0045">Fig&#46; 9</a>&#41;&#46;</p><elsevierMultimedia ident="fig0045"></elsevierMultimedia></span></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Discussion</span><p id="par0280" class="elsevierStylePara elsevierViewall">The primary objective of our study was to examine the impact of mechanical ventilation in the prone position upon mortality in patients with ARDS&#46; Global assessment of the results revealed a nonsignificant tendency to reduce mortality risk in favor of the prone position group&#46; However&#44; on individually analyzing the studies&#44; we found that the most recent trials<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12&#44;14&#44;16</span></a> incorporated a number of changes in both the inclusion criteria and in the prone position protocol&#44; based on the analysis of the probable causes underlying the discouraging results recorded in the earlier studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;13&#44;15</span></a> A first change was the inclusion of more severely compromised patients&#44; with PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>200&#44; while a second change was the prolongation of pronation time to over 16 consecutive hours a day&#46; A third change was the utilization of protective ventilation strategies with a tidal volume of &#60;8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight&#44; the maintenance of a plateau pressure of &#60;30<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; and titration of the optimum PEEP level according to the recommendations of the ARDS network&#46; On examining the studies linearly over time&#44; we observed a tendency to gradually favor the prone position&#44; culminating in the study published by Guerin et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> where a strong reduction in mortality risk was recorded in favor of pronation &#40;HR 0&#46;44&#59; 95&#37;CI&#58; 0&#46;29&#8211;0&#46;67&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001 after 90 days&#41;&#46; These findings are consistent with those of two recent meta-analyses&#46; The first study was carried out by Beitler et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> who conducted a meta-analysis of individual patient data&#44; including the PROSEVA study&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> assessing mortality after 60 days&#44; with the identification of a nonsignificant tendency in favor of pronation &#40;RR&#58; 0&#46;83&#59; 95&#37;CI&#58; 0&#46;68&#8211;1&#46;02&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;073&#41;&#46; The second study was published by Lee et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> based on broader inclusion criteria and a larger number of studies&#44; and identified a global decrease in mortality risk&#44; though with a confidence interval very close to one &#40;OR&#58; 0&#46;77&#59; 95&#37;CI&#58; 0&#46;59&#8211;0&#46;99&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;039&#41;&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">However&#44; interesting data were obtained on stratifying the results by subgroups&#44; supporting our theory regarding the evolution and optimization of the prone position ventilation strategy based on plausible physiology and clear clinical characteristics&#46; Firstly&#44; the utilization of a low tidal volume &#40;&#60;8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight&#41; in patients with ARDS became generalized after publication of the ARDS network study<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#44; which revealed a decrease in mortality risk probably related to the generation of lesser mechanical stress upon the alveolar membrane by preventing overdistension and improving alveolar stability&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> This&#44; being associated to recruitment capacity and homogenization of the distribution of ventilation&#44; flow and airway pressures attributed to pronation&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> probably also produce an additive effect in the prevention and reduction of ventilator-associated lung injury&#46; Thus&#44; on evaluating the subgroup of patients in which a tidal volume of &#60;8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight was used&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;14&#8211;16</span></a> a significant decrease in mortality risk was noted in comparison with the group receiving a greater tidal volume<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;13&#44;15</span></a>&#8211;these findings possibly being attributable to the decrease in ventilator-associated lung injury&#46; Beitler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and Lee et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> also recorded a significant decrease in mortality risk in those studies that used low tidal volumes &#40;RR&#58; 0&#46;66&#59; 95&#37;CI&#58; 0&#46;5&#8211;0&#46;86&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002 and OR&#58; 0&#46;62&#59; 95&#37;CI&#58; 0&#46;48&#8211;0&#46;69&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015&#44; respectively&#41;&#46; Beitler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> in turn performed a metaregression analysis that revealed a dose&#8211;response relationship between the mean basal tidal volume and the relative risk of death after 60 days during pronation&#46; Specifically&#44; a decrease in mean basal tidal volume of 1<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight was seen to be associated to a 16&#46;7&#37; mortality risk&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">The degree of alveolar recruitment in the prone position also requires consideration&#46; Acute respiratory distress syndrome is characterized by disruption of the alveolar-capillary barrier&#44; with increased permeability of the latter and the production of flooding and alveolar edema furthermore associated to the depletion of surfactant&#8211;thus giving rise to alveolar instability and collapse&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Pulmonary involvement is heterogeneous&#44; with well aerated lung regions that participate in gas exchange&#44; and other regions that have collapsed as a result of the overpressure exerted by the interstitial edema and alveolar flooding<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39&#44;40</span></a>&#8211;these mechanisms explaining the decrease in lung volume in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> Pronation makes it possible to recruit these affected zones&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> redistributing and homogenizing ventilation&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> reducing the intrapulmonary shunt effect and improving oxygenation&#44; ventilation and lung mechanics&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> However&#44; the degree of recruitment depends on factors such as the severity of lung involvement&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> the pronation time<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> and the time elapsed from lung injury to patient placement in the prone position&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Although the prone position can effectively increase oxygenation when used several days after onset of the disease&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> its application during the early stages was found to offer betters results&#46; During these early stages&#44; all the conditions favoring the effectiveness of pronation are present&#44; such as alveolar edema&#44; reversible collapse and the absence of pulmonary structural alterations&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> In these stages&#44; the reduction in ventilator-associated lung injury risk probably exceeds that obtained when pronation is used in later stages of ARDS&#44; when the damage has already been caused&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> This has been clearly demonstrated in our study&#44; where the patients placed in the prone position within the first 48<span class="elsevierStyleHsp" style=""></span>h of the evolution of the disease showed a clear protective effect referred to mortality risk&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">In clinical practice&#44; the severity of ARDS has been rated according to the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> though in disorders as complex as this syndrome&#44; the PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> ratio depends on the PEEP level and FiO<span class="elsevierStyleInf">2</span> administered&#44; as well as on the prescribed treatments and&#47;or interventions&#44; the comorbidities&#44; and the innate compensatory mechanisms of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> Despite the presence of these variables&#44; the results obtained allow us to clearly establish that the prone position is indicated in patients with severely impaired oxygenation&#44; as has already been demonstrated in other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;17&#8211;19&#44;21&#8211;23</span></a> Furthermore&#44; prolongation of the prone position to over 12 consecutive hours a day &#40;18<span class="elsevierStyleHsp" style=""></span>h on average&#41; in patients with severe ARDS is a highly recommended strategy&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12&#44;14&#44;16</span></a> It is important to note that in patients with mild ARDS&#44; pronation has not been found to offer clinical advantages and is therefore not advised&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In cases of moderate ARDS&#44; the clinical recommendation is likewise not clear&#44; though the results of the post hoc analysis of a meta-analysis<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> revealed a certain tendency to benefit patients with PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>140&#46; Consequently&#44; when taken in combination with the results of the PROSEVA study&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> these data allow us to consider the use of this strategy in this patient subgroup&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;44</span></a></p><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Adverse events</span><p id="par0305" class="elsevierStylePara elsevierViewall">In general&#44; ventilation in the prone position is safe&#44; and its complications are infrequent&#46; The most common adverse effects are pressure ulcers and orotracheal tube obstruction&#46; Accidental extubation&#44; displacement of the orotracheal tube&#44; the risk of pneumothorax&#44; and venous access loss exhibited a similar distribution between the two groups&#46; The development of ventilator-associated pneumonia &#40;VAP&#41; was not related to pronation&#44; and its frequency was similar to that reported in previous reviews&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Although the incidence of adverse events is low&#44; we think that it is largely conditioned by treating team experience with the prone position&#44; and the existence of guides and protocols with the indications&#44; contraindications and safety measures to be adopted during the procedure&#46;</p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conclusions</span><p id="par0310" class="elsevierStylePara elsevierViewall">The prone position offers clinical benefits such as improved oxygenation&#44; by optimizing lung recruitment and the ventilation&#8211;perfusion ratio&#44; and probably also prevents and reduces ventilator-associated lung injury by homogenizing the stress and strain upon the lung parenchyma&#44; resulting in a decrease in mortality risk&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Based on the results obtained&#44; the prone position can be recommended in patients with severe hypoxemia &#40;PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>100&#41;&#44; associated to a low tidal volume &#40;&#60;8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight&#41;&#44; during a period of over 16<span class="elsevierStyleHsp" style=""></span>h a day&#44; and starting early during the course of the disease &#40;&#60;48<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; These consequently would be the indications and associated strategies to be included in pronation protocols&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Pronation requires no special equipment&#44; but should be carried out by trained personnel and adopting the required safety measures in order to avoid associated complications&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Financial support</span><p id="par0325" class="elsevierStylePara elsevierViewall">The authors declare that no financial support has been received for this study from any government or private organism&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Conflicts of interest</span><p id="par0330" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Prone position and mortality"
              "secciones" => array:8 [
                0 => array:2 [
                  "identificador" => "sec0075"
                  "titulo" => "Global mortality"
                ]
                1 => array:2 [
                  "identificador" => "sec0080"
                  "titulo" => "Mortality and protective ventilation"
                ]
                2 => array:2 [
                  "identificador" => "sec0085"
                  "titulo" => "Mortality and number of hours a day in the prone position"
                ]
                3 => array:2 [
                  "identificador" => "sec0090"
                  "titulo" => "Mortality and start of pronation"
                ]
                4 => array:2 [
                  "identificador" => "sec0095"
                  "titulo" => "Mortality and severity of hypoxemia"
                ]
                5 => array:2 [
                  "identificador" => "sec0100"
                  "titulo" => "Prone position&#44; stay in intensive care and days on mechanical ventilation"
                ]
                6 => array:2 [
                  "identificador" => "sec0105"
                  "titulo" => "Prone position and adverse effects"
                ]
                7 => array:2 [
                  "identificador" => "sec0110"
                  "titulo" => "Assessment of publication bias"
                ]
              ]
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0115"
          "titulo" => "Discussion"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0120"
              "titulo" => "Adverse events"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0125"
          "titulo" => "Conclusions"
        ]
        9 => array:2 [
          "identificador" => "sec0130"
          "titulo" => "Financial support"
        ]
        10 => array:2 [
          "identificador" => "sec0135"
          "titulo" => "Conflicts of interest"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-09-12"
    "fechaAceptado" => "2014-11-04"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec573316"
          "palabras" => array:3 [
            0 => "Respiratory distress syndrome&#44; adult"
            1 => "Prone position"
            2 => "Meta-analysis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec573315"
          "palabras" => array:3 [
            0 => "S&#237;ndrome de dificultad respiratoria del adulto"
            1 => "Posici&#243;n prona"
            2 => "Metan&#225;lisis"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prone position ventilation has been shown to improve oxygenation and ventilatory mechanics in patients with acute respiratory distress syndrome&#46; We evaluated whether prone ventilation reduces the risk of mortality in adult patients with acute respiratory distress syndrome versus supine ventilation&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methodology</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A meta-analysis of randomized controlled trials comparing patients in supine versus prone position was performed&#46; A search was conducted of the Pubmed&#44; Embase&#44; Cochrane Library&#44; and LILACS databases&#46; Mortality&#44; hospital length of stay&#44; days of mechanical ventilation and adverse effects were evaluated&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Seven randomized controlled trials &#40;2119 patients&#41; were included in the analysis&#46; The prone position showed a nonsignificant tendency to reduce mortality &#40;OR&#58; 0&#46;76&#59; 95&#37;CI&#58; 0&#46;54&#8211;1&#46;06&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;11&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 63&#37;&#41;&#46; When stratified by subgroups&#44; a significant decrease was seen in the risk of mortality in patients ventilated with low tidal volume &#40;OR&#58; 0&#46;58&#59; 95&#37;CI&#58; 0&#46;38&#8211;0&#46;87&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 33&#37;&#41;&#44; prolonged pronation &#40;OR&#58; 0&#46;6&#59; 95&#37;CI&#58; 0&#46;43&#8211;0&#46;83&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 27&#37;&#41;&#44; start within the first 48<span class="elsevierStyleHsp" style=""></span>h of disease evolution &#40;OR 0&#46;49&#59; 95&#37;CI 0&#46;35&#8211;0&#46;68&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41; and severe hypoxemia &#40;OR&#58; 0&#46;51&#58; 95&#37;CI&#58; 0&#46;36&#8211;1&#46;25&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#44; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41;&#46; Adverse effects associated with pronation were the development of pressure ulcers and endotracheal tube obstruction&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Prone position ventilation is a safe strategy and reduces mortality in patients with severely impaired oxygenation&#46; It should be started early&#44; for prolonged periods&#44; and should be associated to a protective ventilation strategy&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methodology"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La ventilaci&#243;n en posici&#243;n prona ha demostrado mejorar la oxigenaci&#243;n y la mec&#225;nica pulmonar en pacientes con s&#237;ndrome de dificultad respiratoria aguda&#46; Nosotros evaluamos si la posici&#243;n prona disminuye el riesgo de mortalidad en pacientes adultos con s&#237;ndrome de dificultad respiratoria aguda versus ventilaci&#243;n en posici&#243;n supina&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Metodolog&#237;a</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un metan&#225;lisis de ensayos cl&#237;nicos controlados aleatorizados que compararon pacientes en posici&#243;n prona versus supina&#46; Se realiz&#243; una b&#250;squeda en Pubmed&#44; Embase&#44; Cochrane Library y LILACS&#46; Se evalu&#243; mortalidad&#44; estancia hospitalaria&#44; d&#237;as de ventilaci&#243;n mec&#225;nica y efectos adversos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Siete ensayos cl&#237;nicos controlados aleatorizados &#40;2&#46;119 pacientes&#41; fueron incluidos en el an&#225;lisis&#46; La posici&#243;n prona mostr&#243; una tendencia no significativa a disminuir la mortalidad &#40;OR&#58; 0&#44;76&#59; IC 95&#37;&#58; 0&#44;54&#8211;1&#44;06&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;11&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 63&#37;&#41;&#46; Al estratificar por subgrupos se encontr&#243; una disminuci&#243;n significativa en el riesgo de mortalidad en los pacientes ventilados con volumen corriente bajo &#40;OR&#58; 0&#44;58&#59; IC 95&#37;&#58; 0&#44;38&#8211;0&#44;87&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;009&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 33&#37;&#41;&#44; pronaci&#243;n prolongada &#40;OR&#58; 0&#44;6&#59; IC 95&#37;&#58; 0&#44;43&#8211;0&#44;83&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 27&#37;&#41;&#44; instauraci&#243;n antes de 48<span class="elsevierStyleHsp" style=""></span>h de evoluci&#243;n de la enfermedad &#40;OR&#58; 0&#44;49&#59; IC 95&#37;&#58; 0&#44;35&#8211;0&#44;68&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41; e hipoxemia severa &#40;OR&#58; 0&#44;51&#59; IC 95&#37;&#58; 0&#44;36&#8211;1&#44;25&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> 0&#37;&#41;&#46; Los efectos adversos relacionados con la pronaci&#243;n fueron el desarrollo de &#250;lceras por presi&#243;n y obstrucci&#243;n del tubo orotraqueal&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La ventilaci&#243;n en posici&#243;n prona es una estrategia segura y disminuye la mortalidad en los pacientes con compromiso severo de la oxigenaci&#243;n&#44; debe ser instaurada tempranamente&#44; durante periodos prolongados y asociada a una estrategia de ventilaci&#243;n protectora&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Metodolog&#237;a"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mora-Arteaga JA&#44; Bernal-Ram&#237;rez OJ&#44; Rodr&#237;guez SJ&#46; Efecto de la ventilaci&#243;n mec&#225;nica en posici&#243;n prona en pacientes con s&#237;ndrome de dificultad respiratoria aguda&#46; Una revisi&#243;n sistem&#225;tica y metan&#225;lisis&#46; Med Intensiva&#46; 2015&#59;39&#58;359&#8211;372&#46;</p>"
      ]
    ]
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      0 => array:7 [
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Study screening process&#46; ON&#58; nitric oxide&#46;</p>"
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      1 => array:7 [
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Global mortality and bias risk&#46; Mortality was evaluated up until the end of follow-up in each study&#46; The bias risk of each study was scored as high &#40;&#8722;&#41;&#44; intermediate &#40;&#63;&#41; or low &#40;&#43;&#41;&#46;</p>"
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        "identificador" => "fig0015"
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        "mostrarFloat" => true
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Mortality and protective ventilation&#46; The prone position exerted a protective effect in patients ventilated with a tidal volume &#60;8<span class="elsevierStyleHsp" style=""></span>ml&#47;kg ideal weight&#46;</p>"
        ]
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      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Mortality and hours a day in the prone position&#46; Significant differences were found in favor of the group placed in the prone position during more than 12<span class="elsevierStyleHsp" style=""></span>h a day&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mortality and timing of the start of pronation&#46; Pronation within the first 48<span class="elsevierStyleHsp" style=""></span>h was associated to a decrease in mortality risk&#46;</p>"
        ]
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      5 => array:7 [
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        "etiqueta" => "Figure 6"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Mortality and severity of hypoxemia&#46; Taccone et al&#46; stratified the patients into individuals with moderate or severe hypoxemia&#46; The data of each group were taken separately to the effects of analysis&#46;</p>"
        ]
      ]
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        "etiqueta" => "Figure 7"
        "tipo" => "MULTIMEDIAFIGURA"
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            "imagen" => "gr7.jpeg"
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Ventilation in the prone position&#44; stay in intensive care and days on mechanical ventilation&#46; No significant differences were found between the groups of patients&#46;</p>"
        ]
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      7 => array:7 [
        "identificador" => "fig0040"
        "etiqueta" => "Figure 8"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Ventilation in the prone position and adverse effects&#46; A direct relationship was found between pronation and the risk of pressure ulcers and orotracheal tube obstruction&#46;</p>"
        ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Funnel plot&#46; Visual inspection reveals no selection bias&#46;</p>"
        ]
      ]
      9 => array:7 [
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">NR&#58; not reported&#59; PAOP&#58; pulmonary artery occlusion pressure&#59; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span>&#58; ratio between partial pressure of oxygen in arterial blood and fraction of inspired oxygen&#59; PEEP&#58; positive end-expiratory pressure&#59; TV&#58; tidal volume&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study&#47;characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gatinoni et al&#46; &#40;2001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Guerin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Voggenreiter et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mancebo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Fernandez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Taccone et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gu&#233;rin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Total patients &#40;no&#46;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">304&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">791&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">136&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">342&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">466&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Recruitment period</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">December 1996&#8211;October 1999&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">December 1998&#8211;december 2002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">September 1999&#8211;September 2001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">December 1998&#8211;September 2002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">September 2003&#8211;September 2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">February 2004&#8211;October 2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">January 2008&#8211;July 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Follow-up period</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">180 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Until hospital discharge&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">180 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Inclusion criteria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>200 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>300 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; PAOP<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>300 expected mechanical ventilation time &#62;48<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>200 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>300 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; PAOP<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>200 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; PAOP<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>200 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; PAOP<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>200 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; PAOP<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>18<span class="elsevierStyleHsp" style=""></span>mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>150 with PEEP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#44; TV 6<span class="elsevierStyleHsp" style=""></span>ml&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Mean age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleItalic">Severity &#40;mean&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">127&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">152&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">221&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">146&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">155&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>APACHE <span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>SAPS <span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>SOFA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleItalic">Ventilator settings</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PEEP &#40;cmH<span class="elsevierStyleInf">2</span>O&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tidal volume &#40;ml&#47;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleItalic">Prone position</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Time before pronation &#40;hours&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hours a day in pronation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total days in pronation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pronation suspension criterion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Completion of 10 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Improvement of PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30&#37; with FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60&#37; and PEEP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>8 cmH<span class="elsevierStyleInf">2</span>O&#59; no sepsis or resolution of cause of ventilation failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>300 during &#62;48<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Start of weaning from ventilator&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>250 with PEEP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O during &#62;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution of ventilation failure and&#47;or 28 days from admission to study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>150 PEEP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O and FiO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="8" align="left" valign="top"><span class="elsevierStyleItalic">Methodology</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Allocation concealment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; centralized randomization by telephone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; randomization by sealed and non-transparent envelopes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; centralized randomization by telephone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; centralized randomization by call center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; centralized randomization by telephone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; centralized randomization by web-based system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exclusions after randomization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; one patient in each group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 7 patients in supine group and 4 in prone position group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 2 patients in supine group and 4 in prone position group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; one patient in each group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 5 patients in supine group and 3 in prone position group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Losses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; one patient in each group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 2 patients in prone position group and one in supine group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; one patient in each group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; two patients in each group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Supine to prone cross-over&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 12 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 81 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 5 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 2 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; 20 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Early termination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Summarized characteristics of the studies&#46;</p>"
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
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Article information

ISSN: 21735727
Original language: English

DOI:10.1016/j.medine.2014.11.004

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Year/Month	Html	Pdf	Total

2024 November	13	11	24
2024 October	135	58	193
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2024 March	200	64	264
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2023 August	161	30	191
2023 July	157	62	219
2023 June	131	24	155
2023 May	148	56	204
2023 April	115	53	168
2023 March	161	62	223
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2022 December	148	110	258
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2022 October	193	111	304
2022 September	142	45	187
2022 August	108	96	204
2022 July	109	73	182
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2022 May	156	94	250
2022 April	227	129	356
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2021 December	227	133	360
2021 November	382	175	557
2021 October	381	224	605
2021 September	336	130	466
2021 August	338	151	489
2021 July	349	122	471
2021 June	399	148	547
2021 May	669	210	879
2021 April	2222	511	2733
2021 March	1143	313	1456
2021 February	763	187	950
2021 January	684	132	816
2020 December	726	118	844
2020 November	667	118	785
2020 October	516	141	657
2020 September	409	101	510
2020 August	523	112	635
2020 July	824	178	1002
2020 June	784	217	1001
2020 May	1120	299	1419
2020 April	1967	239	2206
2020 March	1084	139	1223
2020 February	741	127	868
2020 January	489	82	571
2019 December	400	80	480
2019 November	892	136	1028
2019 October	658	93	751
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2019 August	257	66	323
2019 July	169	63	232
2019 June	140	88	228
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2019 February	145	83	228
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2018 May	63	15	78
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2018 March	124	48	172
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2017 September	45	37	82
2017 August	32	13	45
2017 July	52	20	72
2017 June	56	30	86
2017 May	69	29	98
2017 April	78	37	115
2017 March	61	33	94
2017 February	80	10	90
2017 January	24	12	36
2016 December	64	26	90
2016 November	111	25	136
2016 October	118	44	162
2016 September	114	20	134
2016 August	86	10	96
2016 July	40	13	53
2016 February	2	0	2
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