Association between obesity and mortality in adult patients receiving invasive mechanical ventilation: A systematic review and meta-analysis

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Tocalini, A. Vicente, R.L. Amoza, C. García Reid, A.J. Cura, W.A. Tozzi, M. Villarruel, F. Esperón, M.A. Alí, M.N. Novo, S.A. Virgilio" "autores" => array:11 [ 0 => array:4 [ "nombre" => "P." "apellidos" => "Tocalini" "email" => array:1 [ 0 => "pablotocalini@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Vicente" ] 2 => array:2 [ "nombre" => "R.L." "apellidos" => "Amoza" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "García Reid" ] 4 => array:2 [ "nombre" => "A.J." "apellidos" => "Cura" ] 5 => array:2 [ "nombre" => "W.A." "apellidos" => "Tozzi" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "Villarruel" ] 7 => array:2 [ "nombre" => "F." "apellidos" => "Esperón" ] 8 => array:2 [ "nombre" => "M.A." "apellidos" => "Alí" ] 9 => array:2 [ "nombre" => "M.N." "apellidos" => "Novo" ] 10 => array:2 [ "nombre" => "S.A." "apellidos" => "Virgilio" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital General de Agudos Parmenio T. Piñero, Departamento de Diagnóstico y Tratamiento, Servicio de Kinesiología, Ciudad Autónoma de Buenos Aires, Argentina" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Asociación entre obesidad y mortalidad en pacientes adultos que reciben ventilación mecánica invasiva: una revisión sistemática y metaanálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2529 "Ancho" => 2083 "Tamanyo" => 241748 ] ] "descripcion" => array:1 [ "en" => "Flow chart." ] ] ] "textoCompleto" => "IntroductionObesity is a multifactor chronic disease<a class="elsevierStyleCrossRef" href="#bib0195">1</a> defined by the World Health Organization (WHO) as an abnormal or excessive accumulation of fat.<a class="elsevierStyleCrossRef" href="#bib0200">2</a> Actually, it is a public health problem worldwide.<a class="elsevierStyleCrossRef" href="#bib0205">3</a>Due to the growing prevalence and frequent association with other diseases and conditions, obese patients are often hospitalized in the Intensive Care Unit (ICU) where Invasive Mechanical Ventilation (IMV) is one of the most widely used therapeutic options.<a class="elsevierStyleCrossRefs" href="#bib0210">4,5</a> Regardless of the cause for admission, this subgroup of critically ill patients is challenging per se due to their higher morbimortality.<a class="elsevierStyleCrossRef" href="#bib0220">6</a> Controversial results have been found among the various studies that have analyzed the association between obesity and mortality at the ICU setting.<a class="elsevierStyleCrossRefs" href="#bib0210">4,7–13</a>Bercault et al. reported that obesity and IMV are independent risk factors of mortality at the ICU mortality setting (odds ratio [OR] 2.1; 95% confidence interval: 1.2–3.6, P=.007)<a class="elsevierStyleCrossRef" href="#bib0210">4</a> while Solh et al. found this association in the subgroup of patients with morbid obesity.<a class="elsevierStyleCrossRef" href="#bib0225">7</a> Similarly, Goulenok et al. found that a high body mass index (BMI) is a prognostic factor of mortality in critically ill patients.<a class="elsevierStyleCrossRef" href="#bib0230">8</a>In the studies conducted by O’Brien et al., Tremblay, and Frat et al. no correlation between obesity and mortality was found.<a class="elsevierStyleCrossRefs" href="#bib0235">9,10,12</a> Similarly, Anzueto et al. analyzed time variables such as days on IMV, length of the ICU and hospital stays and they did not find any significant differences among the different categories of the BMI.<a class="elsevierStyleCrossRef" href="#bib0245">11</a> However, O’Brien et al. reported lower mortality rates.<a class="elsevierStyleCrossRef" href="#bib0255">13</a>To this day, 7 systematic reviews (SR) that analyzed the correlation between obesity and mortality at the ICU setting have been found showing various results.<a class="elsevierStyleCrossRefs" href="#bib0260">14–20</a> Hogue et al. and Oliveros et al. did not establish any correlations between such variables in critically ill patients.<a class="elsevierStyleCrossRefs" href="#bib0260">14,15</a> However, Falagas et al. reported higher mortality rates in subjects with infections,<a class="elsevierStyleCrossRef" href="#bib0270">16</a> and other authors have described lower mortality rates in septic patients,<a class="elsevierStyleCrossRef" href="#bib0280">18</a> patients with pneumonia,<a class="elsevierStyleCrossRef" href="#bib0275">17</a> and critically ill patients.<a class="elsevierStyleCrossRef" href="#bib0290">20</a>The meta-analyses that study this issue reported statistical heterogeneity and did not take the clinical or methodological characteristics of each of the studies included into consideration. This means that some SRs showed methodological heterogeneity because their meta-analysis considered retrospective and prospective studies together without making any differences among different designs.<a class="elsevierStyleCrossRefs" href="#bib0260">14,15,17,18,20</a> Regarding clinical heterogeneity, some studies used different ways to stratify the BMI including low-body-weight patients in the analysis.<a class="elsevierStyleCrossRef" href="#bib0290">20</a> Other studies analyzed specific subgroups of patients such as patients with pneumonia,<a class="elsevierStyleCrossRef" href="#bib0275">17</a> sepsis, and septic shock.<a class="elsevierStyleCrossRef" href="#bib0280">18</a> Lastly, some of the studies published did not discriminate between patients who received IMV and those who did not.<a class="elsevierStyleCrossRefs" href="#bib0260">14,15</a>Therefore, none of the aforementioned studies has emphasized the impact BMI has on mortality at the ICU setting in obese patients who need IMV. For this reason, we believe it is very important to analyze this subgroup of patients.The hypothesis of our study is that obese adult patients who need IMV have higher mortality rates at the ICU setting compared to non-obese patients.The goal of this SR was to assess whether there is a correlation between obesity (BMI≥30kg/m2) and mortality at the ICU setting in adult patients on IMV.Patients and methodSearch strategy: a systematic review (SR) was conducted of the medical literature available according to the following checklist: Meta-Analyses of Observational Studies Epidemiology (MOOSE).<a class="elsevierStyleCrossRef" href="#bib0295">21</a> The registry took place at the International Prospective Register of Systematic Reviews (PROSPERO) back in March 27, 2017 with code# crd42017059983.<a class="elsevierStyleCrossRef" href="#bib0300">22</a>The search was conducted by an experienced librarian who reviewed the following databases: MEDLINE, Cochrane Library, CINAHL, and OVID (Global Health) without language restriction until February 2017. A specific strategy was established for every particular database (annex 1 of the supplementary data).The data published on gray literature on Google®, GreyNet International, Open Grey, and New York Academy of Medicine Grey Literature Report were reviewed too.A manual search of the article references identified as relevant was conducted. The lead author of the studies reviewed identified as relevant was contacted over the e-mail. When no answer was received or his answer was not consistent with the primary and secondary outcome variables, the study was eliminated since data could not be analyzed.Selection of studies and data miningFour reviewers grouped in pairs identified the studies and conducted an independent examination of the titles and abstracts identified through electronic searches. The complete versions of all potentially relevant studies were recovered. When no agreement was reached between the authors of the pair, a third reviewer from the team of researchers was added to the mix to solve discrepancies.Inclusion criteriaThe primary studies that met the following criteria were included:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">–Comparison between obese patients (BMI≥30kg/m2) versus non-obese patients (BMI<30kg/m2).</li><li class="elsevierStyleListItem" id="lsti0010">–Mortality at the ICU setting reported as the outcome variable.</li><li class="elsevierStyleListItem" id="lsti0015">–Present a population that requires IMV during the ICU stay.</li></ul>Exclusion criteria<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020">–Studies that analyzed the same patient database. Of these, the study whose sample had the smallest size was excluded.</li><li class="elsevierStyleListItem" id="lsti0025">–Studies duplicated in several databases.</li><li class="elsevierStyleListItem" id="lsti0030">–Studies conducted in neonatal or pediatric ICUs.</li></ul>Primary variables of interest<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035">–Mortality at the ICU setting.</li></ul>Secondary variables<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0040">–Duration of IMV: days elapsed since ventilatory support was prescribed until extubation, and lack of ventilatory support for 48h after weaning from ventilatory support.<a class="elsevierStyleCrossRef" href="#bib0305">23</a></li><li class="elsevierStyleListItem" id="lsti0045">–ICU stay: days elapsed since admission until discharge or death.</li><li class="elsevierStyleListItem" id="lsti0050">–Hospital stay: days elapsed since admission until discharge or death at the hospital.</li></ul>Four reviewers grouped in pairs scored the methodological quality of each study included usinfg the Newcastle-Ottawa scale. This scale is a tool used to assess the quality of the observational studies of SRs and meta-analyses.<a class="elsevierStyleCrossRef" href="#bib0310">24</a> Disagreements were solved by consensus.On the other hand, 2 independent reviewers assessed the quality of the evidence of the primary variables using the Grading of Recommendations Assessment Development and Evaluation (GRADE)<a class="elsevierStyleCrossRef" href="#bib0315">25</a> and the GRADEpro Guideline Development Tool (GDT) software. These variables were stratified from low to high quality. Reviewers solved disagreements by consensus.Data synthesis and statistical analysisThe following data from every study were collected: information on the author, year of publication, type of study, results, and other significant characteristics. In order to estimate mortality at the ICU setting, the number of events was registered over the total number of patients. The mean and standard deviation (SD) or median and interquartile range (IQR) of the studies that provided information on the duration of IMV and ICU and hospital stay were registered for every BMI category using the criteria established by the WHO.<a class="elsevierStyleCrossRef" href="#bib0200">2</a> This classification—used and recognized worlwide—considers obese subjects those with BMI≥30kg/m2.The correlation between obesity and mortality at the ICU setting was expressed using the OR with a 95%CI.In order to conduct the meta-analysis, the presence of 3 or more studies that met the inclusion criteria was established as a prerequisite.Statistical heterogeneity was calculated using the chi-square test and the I2 values. According to the latter, heterogeneity was classified as low (<30%), moderate (30–70%), and high (>70%).First, 2 sensitivity analyses were conducted based on the type of study design, and prospective and retrospective studies were assessed in isolation. No thorough analysis was conducted of the latter due to their limitations in the registry of the variables and associated biases. On the other hand, the prospective studies that categorized the BMI were analyzed and the low-body-weight subgroup (BMI<18.5kg/m2) was excluded due to its higher mortality rate.The mortality variable at the ICU setting was analyzed using the fixed effect estimator. In the presence of clinical and methodological heterogeneity the random effect estimator was used. These values were expressed using the forest plot for the variables analyzed. Publication bias was assessed using Begg's test, Egger's test, and the corresponding funnel plot was designed.P values≤.05 were considered statistically significant.The analysis of data was conducted using the RevMan software (Review Manager) version 5.3.5 developed by the Cochrane Group, Review Manager (RevMan) [Computer program]. Version 5.3.5. Copenhaguen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014 y el software STATA versión 13 (StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP.).ResultsThe initial search identified 2163 studies out of which 1543 were reviewed by title and abstract considering that 36 of these came from the manual search. The entire body of 302 articles was assessed, of which 14 met the inclusion criteria for data analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Reasons for excluding articles (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>):<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055">–Studies that did not provide any information on the variables of interest, whether primary or secondary, because the analysis of data would have been impossible.</li><li class="elsevierStyleListItem" id="lsti0060">–Studies not found on the medical literature after reviewing different sources of access to scientific literature.</li><li class="elsevierStyleListItem" id="lsti0065">–Studies whose lead authors were contacted over the e-mail and who did not respond or had not analyzed the study variables.</li><li class="elsevierStyleListItem" id="lsti0070">–All SRs considered secondary studies. However, the references were analyzed to have more information.</li></ul>Characteristics of the studiesTable 1 of the annex (supplementary data) shows the data considered relevant from all the studies included.Regarding the design of the studies analyzed, 6 were prospective and 8 were retrospective studies. Seven of these were conducted in Europe, 2 in North America, and 1 in Asia. In total, 89031 patients who required IMV were included of which 6702 (7.5%) showed BMI≥30kg/m2. Regarding diagnosis at the ICU admission, subjects with acute lung injury, acute respiratory distress syndrome, abdominal hypertension, closed trauma, respiratory failure, and septic shock were included. However, none of the studies included the reason for initiating IMV.Obesity was categorized different depending on the study. Three studies<a class="elsevierStyleCrossRefs" href="#bib0320">26–28</a> used the criteria suggested by the WHO,<a class="elsevierStyleCrossRef" href="#bib0200">2</a> 2<a class="elsevierStyleCrossRefs" href="#bib0255">13,29</a> followed the recommendations established by the National Institutes of Health (NIH),<a class="elsevierStyleCrossRef" href="#bib0195">1</a> 1 study followed the modified NIH recommendations,<a class="elsevierStyleCrossRef" href="#bib0340">30</a> and 6 other studies<a class="elsevierStyleCrossRefs" href="#bib0345">31–36</a> registered it as a dichotomic variable using BMI≥30kg/m2 as a cut-off value for obesity. However, Frat et al. only considered severe obesity for their analysis (BMI≥35kg/m2).<a class="elsevierStyleCrossRef" href="#bib0250">12</a>Regarding the demographic variables, in the studies where the entire population required IMV, males<a class="elsevierStyleCrossRefs" href="#bib0325">27,33,35,37</a> were the predominant sex. Regarding age, 3 studies<a class="elsevierStyleCrossRefs" href="#bib0325">27,35,36</a> used the same statistical estimator (mean±SD). Sasabuchi et al.<a class="elsevierStyleCrossRef" href="#bib0325">27</a> reported that obese patients were younger, similar to what Gong et al.<a class="elsevierStyleCrossRef" href="#bib0370">36</a> reported in morbid obese patients (BMI≥40kg/m2). However, Lam et al. did not any find statistically significant inter-group differences.<a class="elsevierStyleCrossRef" href="#bib0365">35</a>Regarding severity at the ICU admission, the most widely used scoring system was the Simplified Acute Physiologic II (SAPS II)<a class="elsevierStyleCrossRefs" href="#bib0250">12,26,28,29,33,35</a> followed by the Sepsis-Related Organ Failure Assessment (SOFA), the Acute Physiologic and Chronic Health Evaluation II (APACHE II,<a class="elsevierStyleCrossRefs" href="#bib0320">26,33,35</a> and the APACHE III<a class="elsevierStyleCrossRefs" href="#bib0360">34,36</a>).Taking into consideration the studies that used the SAPS II, O’Brien et al. were the only ones to find statistically significant differences in the chances of survival in the subgroup of severely obese patients.<a class="elsevierStyleCrossRef" href="#bib0255">13</a> Among the studies that used the APACHE II score, only Sakr al. observed that the group of severely obese patients showed less severity at admission compared to normal-body-weight patients.<a class="elsevierStyleCrossRef" href="#bib0335">29</a> However, this score was obtained for the entire population of patients regardless of their IMV needs. On the other hand, none of the studies that provided information on severity through the SOFA,<a class="elsevierStyleCrossRefs" href="#bib0250">12,26,33,35</a> and the APACHE III scores<a class="elsevierStyleCrossRefs" href="#bib0360">34,36</a> found statistically significant inter-group differences.Mortality at the Intensive Care Unit<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the distribution of all studies included regarding mortality at the ICU setting. No statistically significant differences were found between obese and nonobese patients [OR, 0.94 (95%CI, 0.81–1.10; P=.45)] expressed through a random effects model. Moderate statistical heterogeneity found (I2=47).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>The forest plot shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> shows the sensitivity analysis based on the study design that included prospective studies. There were no statistically significant differences regarding mortality at the ICU setting between obese and nonobese patients [OR 1.03 (95%CI, 0.85–1.25; P=.74)] expressed through a random effects model. No statistical heterogeneity found (I2=0).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>The forest plot shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a> performed a second sensitivity analysis including all retrospective studies. [OR, 0.91 (95%CI, 073–1.13; P=.38)] expressed through a random effects model with no statistically significant inter-group differences. Statistical heterogeneity found (I2=66%).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>Lastly, a third sensitivity analysis of prospective studies was conducted that eliminated those that included low-body-weight patients (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>) [OR, 1.02 (95%CI, 0.83–1.27; P=.82) expressed through a random effects model with no statistically significant inter-group differences. No statistical heterogeneity found (I2=0).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Time variablesDuration of invasive mechanical ventilationThe duration of IMV has been reported by 5 studies. Duane et al. reported on the mean duration of IMV (in days) and found no statistically significant differences (P=.72).<a class="elsevierStyleCrossRef" href="#bib0350">32</a>Similarly, Frat et al.,<a class="elsevierStyleCrossRef" href="#bib0250">12</a> Tafelski et al.,<a class="elsevierStyleCrossRef" href="#bib0345">31</a> and Gong et al.<a class="elsevierStyleCrossRef" href="#bib0370">36</a> reported on the median duration of IMV (in days) to find no statistically significant differences either: P=.28, P=.374, and P=.6, respectively. The first 2 authors reported on this variable as days on IMV while Gong et al. reported it as IMV-free days.Stay at the Intensive Care UnitEight studies reported on this variable. Duane et al., O’Brien et al., and Lam et al. reported it and expressed it as mean±SD but found no statistically significant differences between the subgroups of obese and nonobese patients.<a class="elsevierStyleCrossRefs" href="#bib0255">13,32,35</a>Frat et al., Sakr et al., Tafelski et al., and Sasabuchi et al. reported it in days and expressed it as median (RIQ), but found no statistically significant differences either.<a class="elsevierStyleCrossRefs" href="#bib0250">12,27,29,31</a>. However, Sasabuchi et al. also drew a comparison between patients with and without need for IMV and obtained a value of 4 days (2–8) versus 1 (1–3), respectively, which was a statistically significant difference (P=.01).<a class="elsevierStyleCrossRef" href="#bib0325">27</a>Lastly, Gong et al. also reported on this variable in days (median) in the following terms: normal-body-weight subgroup, 13 days (7–23); overweight, 10 days (6–19); obese, 15.5 days (7–26.5); severely obese, 13 days (9–26), and found statistically significant differences (P=.02) in the category of obese subjects.<a class="elsevierStyleCrossRef" href="#bib0370">36</a>Hospital stayFive studies reported on this variable. O’Brien et al. and Duane et al. reported it and expressed it as mean days and found no statistically inter-group significant differences.<a class="elsevierStyleCrossRefs" href="#bib0255">13,32</a>Other authors reported on this variable in days and expressed it as median. Lam et al. found no statistically significant inter-group differences (P=.75),<a class="elsevierStyleCrossRef" href="#bib0365">35</a> but Gong et al. found 18 days (6–34) in the low-body-weight subgroup, 20 days (10–55) in the normal-body-weight subgroup, 16 days (9–39) in the overweight group, 27 days (12–27) in the obese group, and 28 days (12–60) in severely obese subjects obtaining statistical significance for obese and severely obese groups (P=.007).<a class="elsevierStyleCrossRef" href="#bib0370">36</a> Lastly, Sasabuchi et al. found no statistically significant inter-group differences and longer hospital stays compared to the subgroup of patients who did not require IMV (P=.001).<a class="elsevierStyleCrossRef" href="#bib0325">27</a>Assessment of methodological qualityThe Newcastle-Ottawa scale was used to assess methodological quality in 3 domains: the selection of study groups, group comparability, and quality exposing information (for case studies and controls) or results (for cohort studies).<a class="elsevierStyleCrossRef" href="#bib0310">24</a>As Table 2 of the annex (supplementary data) shows, the prospective study that scored the highest points was the study conducted by Gong et al.,<a class="elsevierStyleCrossRef" href="#bib0370">36</a> and the retrospective design studies that scored the most points were the studies conducted by O’Brien et al.,<a class="elsevierStyleCrossRef" href="#bib0255">13</a> Lam et al.,<a class="elsevierStyleCrossRef" href="#bib0365">35</a> Sasabuchi et al.,<a class="elsevierStyleCrossRef" href="#bib0325">27</a> and Wurzinger et al. (annex, Table 3).<a class="elsevierStyleCrossRef" href="#bib0330">28</a> The main flaws found in prospective studies were the presence of result of interest at the beginning of the study and the lack of proper cohort follow-up. The main flaws found in retrospective studies were the lack of non-response rate.Assessment of the quality of evidenceThe GRADE score<a class="elsevierStyleCrossRef" href="#bib0315">25</a> was used to assess the 14 studies included in this SR. This score reported low quality of evidence for the mortality variable at the ICU setting (annex, Table 4).Publication biasThe funnel plot visual inspection assessed mortality at the ICU setting showing no asymmetry (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>), which was consistent with the results obtained in Begg's test=.956 (P=.35) and Egger's test=.876 (P=.45) without statistically significant differences.<elsevierMultimedia ident="fig0030"></elsevierMultimedia>DiscussionThe objective of this study was to describe the correlation between the mortality variable at the ICU setting and obese patients requiring IMV. Unlike the reviewed medical literature, this SR focused exclusively on this critical population and found no statistically significant differences between this subgroup mortality and nonobese subjects.The lack of a statistically significant association between the obesity variable and mortality at the ICU setting is consistent with the studies conducted by Hogue et al.,<a class="elsevierStyleCrossRef" href="#bib0260">14</a> and Oliveros et al.<a class="elsevierStyleCrossRef" href="#bib0265">15</a> However, these authors did not include in their population subjects requiring IMV only.Contrary to the findings of this SR, Cai et al. and Pepper et al. reported on the lower mortality rate of obese patients.<a class="elsevierStyleCrossRefs" href="#bib0275">17,18</a>. If we analyze the results from their studies, we will see statistical heterogeneity added to the fact that not all the patients included received IMV. Similarly, Akinnusi et al. concluded that subjects with grade i and ii obesity also had lower mortality rates maybe due to a probable protective effect.<a class="elsevierStyleCrossRef" href="#bib0290">20</a> However, this conclusion is consistent with the results found on in-hospital mortality and not with ICU mortality (that does not show any statistically significant inter-group differences).On the other hand, the SR of the study conducted by Falagas et al. reported higher mortality rates in the subgroup of obese patients.<a class="elsevierStyleCrossRef" href="#bib0270">16</a> The authors based their conclusion on the results from 2 out of the 5 studies included. However, this statement is not backed with a meta-analysis.In our SR, the meta-analysis of time variables could not be conducted for several reasons: lack of registry in certain studies; different methodological designs; different statistical estimators<a class="elsevierStyleCrossRefs" href="#bib0250">12,31,32,36,37</a> and incorrect use of these estimators<a class="elsevierStyleCrossRef" href="#bib0350">32</a>; and lack of response from the authors contacted, among others.Regarding the BMI, not all studies categorized it the same way: some conducted data mining<a class="elsevierStyleCrossRefs" href="#bib0320">26,28</a> while in others the measurement method<a class="elsevierStyleCrossRef" href="#bib0365">35</a> was not specified or was conducted after IMV.<a class="elsevierStyleCrossRef" href="#bib0340">30</a> We should mention here that only O’Brien et al. took into consideration the patient's dry weight.<a class="elsevierStyleCrossRef" href="#bib0340">30</a> This BMI measurement bias may have impacted our analysis, but we did not have any tools available to limit the effects of this impact.When conducting the meta-analyse of the mortality variable in the ICU setting from all the studies included, we saw clinical, statistical, and methodological heterogeneity. For this reason, it was decided to conduct a sensitivity analysis excluding retrospective studies to restrict the limitations seen when measuring weight, height, and categorizing BMI. As a result, both groups had the same risk of mortality at the ICU setting.To reduce clinical heterogeneity, a second sensitivity analysis was conducted and the prospective studies that analyzed the low-body-weight subgroup (BMI<18.5kg/m2) were excluded since evidence shows that this subgroup has higher mortality rates.<a class="elsevierStyleCrossRef" href="#bib0335">29</a> As in the aforementioned analysis, the result showed no differences regarding mortality between obese and nonobese patients receiving IMV in the ICU setting.As it is the case with other reviews<a class="elsevierStyleCrossRefs" href="#bib0260">14,17</a> the Newcastle-Ottawa scale<a class="elsevierStyleCrossRef" href="#bib0310">24</a> was the tool of choice to assess the quality of observational studies.<a class="elsevierStyleCrossRef" href="#bib0260">14</a> However, the lack of rigorous manuals makes the interpretation of this tool by the user a difficult task.<a class="elsevierStyleCrossRef" href="#bib0380">38</a>On the other hand, the quality of evidence was assessed using the GRADE score<a class="elsevierStyleCrossRef" href="#bib0315">25</a> since it is mandatory for new reviews and is applied on nonrandomized trials such as those included in this review. The 14 studies included were analyzed for the main result variable and the quality of evidence found was low.The quality of evidence of time variables was not assessed using this scale since they were not meta-analyzed.LimitationsThe subgroup comparison of normal-body-weight subjects (BMI 18.5–24.99kg/m2) versus obese subjects (BMI≥30kg/m2) was not possible because not all primary studies stratified it this way. Also, because the author we contacted over the e-mail did not get back to us.We could not conduct a meta-regression analysis to assess how mortality behaves in both groups. Also, we did not assess the influence of the variables that may be confounding factors such as age, underlying conditions, reason for IMV or severity of patients at the ICU admission. The problem here was that not all studies described these data and those that described them did it in a different way.Regarding the tool used to assess the study methodological quality, no recommendation advocates for its reliability or validity. It does not stratify studies based on methodological quality either.ConclusionThis SR found no correlation between the subgroup of obese adult patients who received IMV and mortality at the ICU setting.The studies included did not allow us to analyze the demographic and time variables because of the different ways the authors expressed such variables and the low quality of evidence available.We believe it is essential to achieve consensus in future studies to have a more operative registry of such variables so that the conclusions drawn can be more solid.Conflict of interestNone of the aforementioned authors declared any conflicts of interest whatsoever." 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DesignSystematic review with meta-analysis. ScopeICU. Data sourceA search was made in MEDLINE, Cochrane Library, CINAHL and Global Health databases without language restriction, until February 21, 2017. Selection of studiesStudies that reported mortality in the ICU in obese versus non-obese patients who received IMV were included. Main variablesMortality in the ICU. Results2163 articles were found, of which 14 studies were included. No statistically significant differences were found between obese and non-obese patients with respect to the variable mortality in the ICU (OR: 0.94, 95% CI: 0.81–1.10, P=.45). ConclusionNo relationship was found between the subgroup of obese adult patients receiving IMV and the mortality variable in the ICU." "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Scope" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Data source" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Selection of studies" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Main variables" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoEvaluar si existe asociación entre obesidad y mortalidad en la Unidad de Cuidados Intensivos (UCI) en pacientes adultos que reciben ventilación mecánica invasiva. DiseñoRevisión sistemática con metaanálisis. ÁmbitoUCI. Fuente de datosSe realizó una búsqueda en las bases de datos MEDLINE, Cochrane Library, CINAHL y Global Health sin restricción de lenguaje, hasta el 21 de febrero del año 2017. Selección de estudiosSe incluyeron estudios que informaron mortalidad en UCI en pacientes obesos versus no obesos que recibieron VMI. Variables principalMortalidad en UCI. ResultadosSe hallaron 2.163 artículos, de los cuales se incluyeron 14 estudios. No se encontraron diferencias estadísticamente significativas entre los pacientes obesos y no obesos respecto a la variable mortalidad en UCI (odds ratio: 0,94; intervalo de confianza del 95%: 0,81-1,10; p=0,45). ConclusiónNo se halló relación entre el subgrupo de pacientes adultos obesos que reciben VMI y la variable mortalidad en UCI." "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Fuente de datos" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Selección de estudios" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Variables principal" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Tocalini P, Vicente A, Amoza RL, García Reid C, Cura AJ, Tozzi WA, et al. Asociación entre obesidad y mortalidad en pacientes adultos que reciben ventilación mecánica invasiva: una revisión sistemática y metaanálisis. Med Intensiva. 2020;44:18–26." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0120" ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2529 "Ancho" => 2083 "Tamanyo" => 241748 ] ] "descripcion" => array:1 [ "en" => "Flow chart." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1319 "Ancho" => 2917 "Tamanyo" => 314625 ] ] "descripcion" => array:1 [ "en" => "Forest plot of all the studies included regarding the mortality variable at the ICU setting. BMI, body mass index." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 860 "Ancho" => 2333 "Tamanyo" => 177000 ] ] "descripcion" => array:1 [ "en" => "Forest plot of the mortality variable at the ICU setting of all prospective studies." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 874 "Ancho" => 2333 "Tamanyo" => 205351 ] ] "descripcion" => array:1 [ "en" => "Forest plot of the mortality variable at the ICU setting of all retrospective studies." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 766 "Ancho" => 2099 "Tamanyo" => 138903 ] ] "descripcion" => array:1 [ "en" => "Forest plot of the mortality variable at the ICU setting of prospective studies without the subgroup of low-body-weight patients (MBI 18.5–29.9kg/m2)." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1307 "Ancho" => 2097 "Tamanyo" => 50427 ] ] "descripcion" => array:1 [ "en" => "Funnel plot for the assessment of publication bias. 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Association between obesity and mortality in adult patients receiving invasive mechanical ventilation: A systematic review and meta-analysis

Asociación entre obesidad y mortalidad en pacientes adultos que reciben ventilación mecánica invasiva: una revisión sistemática y metaanálisis

P. Tocalini

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pablotocalini@hotmail.com

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, A. Vicente, R.L. Amoza, C. García Reid, A.J. Cura, W.A. Tozzi, M. Villarruel, F. Esperón, M.A. Alí, M.N. Novo, S.A. Virgilio

Hospital General de Agudos Parmenio T. Piñero, Departamento de Diagnóstico y Tratamiento, Servicio de Kinesiología, Ciudad Autónoma de Buenos Aires, Argentina

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is one of the most widely used therapeutic options&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">4&#44;5</span></a> Regardless of the cause for admission&#44; this subgroup of critically ill patients is challenging per se due to their higher morbimortality&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">6</span></a> Controversial results have been found among the various studies that have analyzed the association between obesity and mortality at the ICU setting&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">4&#44;7&#8211;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Bercault et al&#46; reported that obesity and IMV are independent risk factors of mortality at the ICU mortality setting &#40;odds ratio &#91;OR&#93; 2&#46;1&#59; 95&#37; confidence interval&#58; 1&#46;2&#8211;3&#46;6&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">4</span></a> while Solh et al&#46; found this association in the subgroup of patients with morbid obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">7</span></a> Similarly&#44; Goulenok et al&#46; found that a high body mass index &#40;BMI&#41; is a prognostic factor of mortality in critically ill patients&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In the studies conducted by O&#8217;Brien et al&#46;&#44; Tremblay&#44; and Frat et al&#46; no correlation between obesity and mortality was found&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">9&#44;10&#44;12</span></a> Similarly&#44; Anzueto et al&#46; analyzed time variables such as days on IMV&#44; length of the ICU and hospital stays and they did not find any significant differences among the different categories of the BMI&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">11</span></a> However&#44; O&#8217;Brien et al&#46; reported lower mortality rates&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">13</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">To this day&#44; 7 systematic reviews &#40;SR&#41; that analyzed the correlation between obesity and mortality at the ICU setting have been found showing various results&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">14&#8211;20</span></a> Hogue et al&#46; and Oliveros et al&#46; did not establish any correlations between such variables in critically ill patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">14&#44;15</span></a> However&#44; Falagas et al&#46; reported higher mortality rates in subjects with infections&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">16</span></a> and other authors have described lower mortality rates in septic patients&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">18</span></a> patients with pneumonia&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">17</span></a> and critically ill patients&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">20</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The meta-analyses that study this issue reported statistical heterogeneity and did not take the clinical or methodological characteristics of each of the studies included into consideration&#46; This means that some SRs showed methodological heterogeneity because their meta-analysis considered retrospective and prospective studies together without making any differences among different designs&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">14&#44;15&#44;17&#44;18&#44;20</span></a> Regarding clinical heterogeneity&#44; some studies used different ways to stratify the BMI including low-body-weight patients in the analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">20</span></a> Other studies analyzed specific subgroups of patients such as patients with pneumonia&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">17</span></a> sepsis&#44; and septic shock&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">18</span></a> Lastly&#44; some of the studies published did not discriminate between patients who received IMV and those who did not&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Therefore&#44; none of the aforementioned studies has emphasized the impact BMI has on mortality at the ICU setting in obese patients who need IMV&#46; For this reason&#44; we believe it is very important to analyze this subgroup of patients&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The hypothesis of our study is that obese adult patients who need IMV have higher mortality rates at the ICU setting compared to non-obese patients&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The goal of this SR was to assess whether there is a correlation between obesity &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; and mortality at the ICU setting in adult patients on IMV&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patients and method</span><p id="par0050" class="elsevierStylePara elsevierViewall">Search strategy&#58; a systematic review &#40;SR&#41; was conducted of the medical literature available according to the following checklist&#58; Meta-Analyses of Observational Studies Epidemiology &#40;MOOSE&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">21</span></a> The registry took place at the International Prospective Register of Systematic Reviews &#40;PROSPERO&#41; back in March 27&#44; 2017 with code&#35; crd42017059983&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">22</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The search was conducted by an experienced librarian who reviewed the following databases&#58; MEDLINE&#44; Cochrane Library&#44; CINAHL&#44; and OVID &#40;Global Health&#41; without language restriction until February 2017&#46; A specific strategy was established for every particular database &#40;annex 1 of the supplementary data&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The data published on gray literature on Google&#174;&#44; GreyNet International&#44; Open Grey&#44; and New York Academy of Medicine Grey Literature Report were reviewed too&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A manual search of the article references identified as relevant was conducted&#46; The lead author of the studies reviewed identified as relevant was contacted over the e-mail&#46; When no answer was received or his answer was not consistent with the primary and secondary outcome variables&#44; the study was eliminated since data could not be analyzed&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Selection of studies and data mining</span><p id="par0070" class="elsevierStylePara elsevierViewall">Four reviewers grouped in pairs identified the studies and conducted an independent examination of the titles and abstracts identified through electronic searches&#46; The complete versions of all potentially relevant studies were recovered&#46; When no agreement was reached between the authors of the pair&#44; a third reviewer from the team of researchers was added to the mix to solve discrepancies&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Inclusion criteria</span><p id="par0075" class="elsevierStylePara elsevierViewall">The primary studies that met the following criteria were included&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8211;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Comparison between obese patients &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; versus non-obese patients &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8211;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Mortality at the ICU setting reported as the outcome variable&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8211;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Present a population that requires IMV during the ICU stay&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Exclusion criteria</span><p id="par0095" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8211;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Studies that analyzed the same patient database&#46; Of these&#44; the study whose sample had the smallest size was excluded&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8211;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Studies duplicated in several databases&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8211;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Studies conducted in neonatal or pediatric ICUs&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Primary variables of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8211;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Mortality at the ICU setting&#46;</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Secondary variables</span><p id="par0125" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8211;</span><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Duration of IMV&#58;</span> days elapsed since ventilatory support was prescribed until extubation&#44; and lack of ventilatory support for 48<span class="elsevierStyleHsp" style=""></span>h after weaning from ventilatory support&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a></p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8211;</span><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">ICU stay&#58;</span> days elapsed since admission until discharge or death&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8211;</span><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Hospital stay&#58;</span> days elapsed since admission until discharge or death at the hospital&#46;</p></li></ul></p><p id="par0145" class="elsevierStylePara elsevierViewall">Four reviewers grouped in pairs scored the methodological quality of each study included usinfg the Newcastle-Ottawa scale&#46; This scale is a tool used to assess the quality of the observational studies of SRs and meta-analyses&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">24</span></a> Disagreements were solved by consensus&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">On the other hand&#44; 2 independent reviewers assessed the quality of the evidence of the primary variables using the Grading of Recommendations Assessment Development and Evaluation &#40;GRADE&#41;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">25</span></a> and the GRADEpro Guideline Development Tool &#40;GDT&#41; software&#46; These variables were stratified from low to high quality&#46; Reviewers solved disagreements by consensus&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Data synthesis and statistical analysis</span><p id="par0155" class="elsevierStylePara elsevierViewall">The following data from every study were collected&#58; information on the author&#44; year of publication&#44; type of study&#44; results&#44; and other significant characteristics&#46; In order to estimate mortality at the ICU setting&#44; the number of events was registered over the total number of patients&#46; The mean and standard deviation &#40;SD&#41; or median and interquartile range &#40;IQR&#41; of the studies that provided information on the duration of IMV and ICU and hospital stay were registered for every BMI category using the criteria established by the WHO&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">2</span></a> This classification&#8212;used and recognized worlwide&#8212;considers obese subjects those with BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The correlation between obesity and mortality at the ICU setting was expressed using the OR with a 95&#37;CI&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In order to conduct the meta-analysis&#44; the presence of 3 or more studies that met the inclusion criteria was established as a prerequisite&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Statistical heterogeneity was calculated using the chi-square test and the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> values&#46; According to the latter&#44; heterogeneity was classified as low &#40;&#60;30&#37;&#41;&#44; moderate &#40;30&#8211;70&#37;&#41;&#44; and high &#40;&#62;70&#37;&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">First&#44; 2 sensitivity analyses were conducted based on the type of study design&#44; and prospective and retrospective studies were assessed in isolation&#46; No thorough analysis was conducted of the latter due to their limitations in the registry of the variables and associated biases&#46; On the other hand&#44; the prospective studies that categorized the BMI were analyzed and the low-body-weight subgroup &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>18&#46;5<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; was excluded due to its higher mortality rate&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The mortality variable at the ICU setting was analyzed using the fixed effect estimator&#46; In the presence of clinical and methodological heterogeneity the random effect estimator was used&#46; These values were expressed using the forest plot for the variables analyzed&#46; Publication bias was assessed using Begg&#39;s test&#44; Egger&#39;s test&#44; and the corresponding funnel plot was designed&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">P</span> values<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#46;05 were considered statistically significant&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The analysis of data was conducted using the RevMan software &#40;Review Manager&#41; version 5&#46;3&#46;5 developed by the Cochrane Group&#44; Review Manager &#40;RevMan&#41; &#91;Computer program&#93;&#46; Version 5&#46;3&#46;5&#46; Copenhaguen&#58; The Nordic Cochrane Centre&#44; The Cochrane Collaboration&#44; 2014 y el software STATA versi&#243;n 13 &#40;StataCorp&#46; 2013&#46; Stata Statistical Software&#58; Release 13&#46; College Station&#44; TX&#58; StataCorp LP&#46;&#41;&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Results</span><p id="par0195" class="elsevierStylePara elsevierViewall">The initial search identified 2163 studies out of which 1543 were reviewed by title and abstract considering that 36 of these came from the manual search&#46; The entire body of 302 articles was assessed&#44; of which 14 met the inclusion criteria for data analysis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0200" class="elsevierStylePara elsevierViewall">Reasons for excluding articles &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8211;</span><p id="par0205" class="elsevierStylePara elsevierViewall">Studies that did not provide any information on the variables of interest&#44; whether primary or secondary&#44; because the analysis of data would have been impossible&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8211;</span><p id="par0210" class="elsevierStylePara elsevierViewall">Studies not found on the medical literature after reviewing different sources of access to scientific literature&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8211;</span><p id="par0215" class="elsevierStylePara elsevierViewall">Studies whose lead authors were contacted over the e-mail and who did not respond or had not analyzed the study variables&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8211;</span><p id="par0220" class="elsevierStylePara elsevierViewall">All SRs considered secondary studies&#46; However&#44; the references were analyzed to have more information&#46;</p></li></ul></p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Characteristics of the studies</span><p id="par0225" class="elsevierStylePara elsevierViewall">Table 1 of the annex &#40;supplementary data&#41; shows the data considered relevant from all the studies included&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Regarding the design of the studies analyzed&#44; 6 were prospective and 8 were retrospective studies&#46; Seven of these were conducted in Europe&#44; 2 in North America&#44; and 1 in Asia&#46; In total&#44; 89<span class="elsevierStyleHsp" style=""></span>031 patients who required IMV were included of which 6702 &#40;7&#46;5&#37;&#41; showed BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46; Regarding diagnosis at the ICU admission&#44; subjects with acute lung injury&#44; acute respiratory distress syndrome&#44; abdominal hypertension&#44; closed trauma&#44; respiratory failure&#44; and septic shock were included&#46; However&#44; none of the studies included the reason for initiating IMV&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Obesity was categorized different depending on the study&#46; Three studies<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">26&#8211;28</span></a> used the criteria suggested by the WHO&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">2</span></a> 2<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">13&#44;29</span></a> followed the recommendations established by the National Institutes of Health &#40;NIH&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">1</span></a> 1 study followed the modified NIH recommendations&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">30</span></a> and 6 other studies<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">31&#8211;36</span></a> registered it as a dichotomic variable using BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> as a cut-off value for obesity&#46; However&#44; Frat et al&#46; only considered severe obesity for their analysis &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>35<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">12</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">Regarding the demographic variables&#44; in the studies where the entire population required IMV&#44; males<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">27&#44;33&#44;35&#44;37</span></a> were the predominant sex&#46; Regarding age&#44; 3 studies<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">27&#44;35&#44;36</span></a> used the same statistical estimator &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&#46; Sasabuchi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">27</span></a> reported that obese patients were younger&#44; similar to what Gong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">36</span></a> reported in morbid obese patients &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46; However&#44; Lam et al&#46; did not any find statistically significant inter-group differences&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">35</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Regarding severity at the ICU admission&#44; the most widely used scoring system was the Simplified Acute Physiologic II &#40;SAPS II&#41;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;26&#44;28&#44;29&#44;33&#44;35</span></a> followed by the Sepsis-Related Organ Failure Assessment &#40;SOFA&#41;&#44; the Acute Physiologic and Chronic Health Evaluation II &#40;APACHE II&#44;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">26&#44;33&#44;35</span></a> and the APACHE III<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">34&#44;36</span></a>&#41;&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Taking into consideration the studies that used the SAPS II&#44; O&#8217;Brien et al&#46; were the only ones to find statistically significant differences in the chances of survival in the subgroup of severely obese patients&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">13</span></a> Among the studies that used the APACHE II score&#44; only Sakr al&#46; observed that the group of severely obese patients showed less severity at admission compared to normal-body-weight patients&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a> However&#44; this score was obtained for the entire population of patients regardless of their IMV needs&#46; On the other hand&#44; none of the studies that provided information on severity through the SOFA&#44;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;26&#44;33&#44;35</span></a> and the APACHE III scores<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">34&#44;36</span></a> found statistically significant inter-group differences&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Mortality at the Intensive Care Unit</span><p id="par0255" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows the distribution of all studies included regarding mortality at the ICU setting&#46; No statistically significant differences were found between obese and nonobese patients &#91;OR&#44; 0&#46;94 &#40;95&#37;CI&#44; 0&#46;81&#8211;1&#46;10&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;45&#41;&#93; expressed through a random effects model&#46; Moderate statistical heterogeneity found &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0260" class="elsevierStylePara elsevierViewall">The forest plot shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> shows the sensitivity analysis based on the study design that included prospective studies&#46; There were no statistically significant differences regarding mortality at the ICU setting between obese and nonobese patients &#91;OR 1&#46;03 &#40;95&#37;CI&#44; 0&#46;85&#8211;1&#46;25&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;74&#41;&#93; expressed through a random effects model&#46; No statistical heterogeneity found &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0265" class="elsevierStylePara elsevierViewall">The forest plot shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a> performed a second sensitivity analysis including all retrospective studies&#46; &#91;OR&#44; 0&#46;91 &#40;95&#37;CI&#44; 073&#8211;1&#46;13&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;38&#41;&#93; expressed through a random effects model with no statistically significant inter-group differences&#46; Statistical heterogeneity found &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>66&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0270" class="elsevierStylePara elsevierViewall">Lastly&#44; a third sensitivity analysis of prospective studies was conducted that eliminated those that included low-body-weight patients &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41; &#91;OR&#44; 1&#46;02 &#40;95&#37;CI&#44; 0&#46;83&#8211;1&#46;27&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;82&#41; expressed through a random effects model with no statistically significant inter-group differences&#46; No statistical heterogeneity found &#40;<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Time variables</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Duration of invasive mechanical ventilation</span><p id="par0275" class="elsevierStylePara elsevierViewall">The duration of IMV has been reported by 5 studies&#46; Duane et al&#46; reported on the mean duration of IMV &#40;in days&#41; and found no statistically significant differences &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;72&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">Similarly&#44; Frat et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">12</span></a> Tafelski et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">31</span></a> and Gong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">36</span></a> reported on the median duration of IMV &#40;in days&#41; to find no statistically significant differences either&#58; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;28&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;374&#44; and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;6&#44; respectively&#46; The first 2 authors reported on this variable as days on IMV while Gong et al&#46; reported it as IMV-free days&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Stay at the Intensive Care Unit</span><p id="par0285" class="elsevierStylePara elsevierViewall">Eight studies reported on this variable&#46; Duane et al&#46;&#44; O&#8217;Brien et al&#46;&#44; and Lam et al&#46; reported it and expressed it as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD but found no statistically significant differences between the subgroups of obese and nonobese patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">13&#44;32&#44;35</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">Frat et al&#46;&#44; Sakr et al&#46;&#44; Tafelski et al&#46;&#44; and Sasabuchi et al&#46; reported it in days and expressed it as median &#40;RIQ&#41;&#44; but found no statistically significant differences either&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;27&#44;29&#44;31</span></a>&#46; However&#44; Sasabuchi et al&#46; also drew a comparison between patients with and without need for IMV and obtained a value of 4 days &#40;2&#8211;8&#41; versus 1 &#40;1&#8211;3&#41;&#44; respectively&#44; which was a statistically significant difference &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">27</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Lastly&#44; Gong et al&#46; also reported on this variable in days &#40;median&#41; in the following terms&#58; normal-body-weight subgroup&#44; 13 days &#40;7&#8211;23&#41;&#59; overweight&#44; 10 days &#40;6&#8211;19&#41;&#59; obese&#44; 15&#46;5 days &#40;7&#8211;26&#46;5&#41;&#59; severely obese&#44; 13 days &#40;9&#8211;26&#41;&#44; and found statistically significant differences &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;02&#41; in the category of obese subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Hospital stay</span><p id="par0300" class="elsevierStylePara elsevierViewall">Five studies reported on this variable&#46; O&#8217;Brien et al&#46; and Duane et al&#46; reported it and expressed it as mean days and found no statistically inter-group significant differences&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">13&#44;32</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Other authors reported on this variable in days and expressed it as median&#46; Lam et al&#46; found no statistically significant inter-group differences &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;75&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">35</span></a> but Gong et al&#46; found 18 days &#40;6&#8211;34&#41; in the low-body-weight subgroup&#44; 20 days &#40;10&#8211;55&#41; in the normal-body-weight subgroup&#44; 16 days &#40;9&#8211;39&#41; in the overweight group&#44; 27 days &#40;12&#8211;27&#41; in the obese group&#44; and 28 days &#40;12&#8211;60&#41; in severely obese subjects obtaining statistical significance for obese and severely obese groups &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">36</span></a> Lastly&#44; Sasabuchi et al&#46; found no statistically significant inter-group differences and longer hospital stays compared to the subgroup of patients who did not require IMV &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">27</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Assessment of methodological quality</span><p id="par0310" class="elsevierStylePara elsevierViewall">The Newcastle-Ottawa scale was used to assess methodological quality in 3 domains&#58; the selection of study groups&#44; group comparability&#44; and quality exposing information &#40;for case studies and controls&#41; or results &#40;for cohort studies&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">24</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">As Table 2 of the annex &#40;supplementary data&#41; shows&#44; the prospective study that scored the highest points was the study conducted by Gong et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">36</span></a> and the retrospective design studies that scored the most points were the studies conducted by O&#8217;Brien et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">13</span></a> Lam et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">35</span></a> Sasabuchi et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">27</span></a> and Wurzinger et al&#46; &#40;annex&#44; Table 3&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">28</span></a> The main flaws found in prospective studies were the presence of result of interest at the beginning of the study and the lack of proper cohort follow-up&#46; The main flaws found in retrospective studies were the lack of non-response rate&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Assessment of the quality of evidence</span><p id="par0320" class="elsevierStylePara elsevierViewall">The GRADE score<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">25</span></a> was used to assess the 14 studies included in this SR&#46; This score reported low quality of evidence for the mortality variable at the ICU setting &#40;annex&#44; Table 4&#41;&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Publication bias</span><p id="par0325" class="elsevierStylePara elsevierViewall">The funnel plot visual inspection assessed mortality at the ICU setting showing no asymmetry &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#44; which was consistent with the results obtained in Begg&#39;s test<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;956 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;35&#41; and Egger&#39;s test<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;876 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;45&#41; without statistically significant differences&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Discussion</span><p id="par0330" class="elsevierStylePara elsevierViewall">The objective of this study was to describe the correlation between the mortality variable at the ICU setting and obese patients requiring IMV&#46; Unlike the reviewed medical literature&#44; this SR focused exclusively on this critical population and found no statistically significant differences between this subgroup mortality and nonobese subjects&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall">The lack of a statistically significant association between the obesity variable and mortality at the ICU setting is consistent with the studies conducted by Hogue et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">14</span></a> and Oliveros et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">15</span></a> However&#44; these authors did not include in their population subjects requiring IMV only&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">Contrary to the findings of this SR&#44; Cai et al&#46; and Pepper et al&#46; reported on the lower mortality rate of obese patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; If we analyze the results from their studies&#44; we will see statistical heterogeneity added to the fact that not all the patients included received IMV&#46; Similarly&#44; Akinnusi et al&#46; concluded that subjects with grade <span class="elsevierStyleSmallCaps">i</span> and <span class="elsevierStyleSmallCaps">ii</span> obesity also had lower mortality rates maybe due to a probable protective effect&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">20</span></a> However&#44; this conclusion is consistent with the results found on in-hospital mortality and not with ICU mortality &#40;that does not show any statistically significant inter-group differences&#41;&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">On the other hand&#44; the SR of the study conducted by Falagas et al&#46; reported higher mortality rates in the subgroup of obese patients&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">16</span></a> The authors based their conclusion on the results from 2 out of the 5 studies included&#46; However&#44; this statement is not backed with a meta-analysis&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">In our SR&#44; the meta-analysis of time variables could not be conducted for several reasons&#58; lack of registry in certain studies&#59; different methodological designs&#59; different statistical estimators<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;31&#44;32&#44;36&#44;37</span></a> and incorrect use of these estimators<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a>&#59; and lack of response from the authors contacted&#44; among others&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Regarding the BMI&#44; not all studies categorized it the same way&#58; some conducted data mining<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">26&#44;28</span></a> while in others the measurement method<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">35</span></a> was not specified or was conducted after IMV&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">30</span></a> We should mention here that only O&#8217;Brien et al&#46; took into consideration the patient&#39;s dry weight&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">30</span></a> This BMI measurement bias may have impacted our analysis&#44; but we did not have any tools available to limit the effects of this impact&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">When conducting the meta-analyse of the mortality variable in the ICU setting from all the studies included&#44; we saw clinical&#44; statistical&#44; and methodological heterogeneity&#46; For this reason&#44; it was decided to conduct a sensitivity analysis excluding retrospective studies to restrict the limitations seen when measuring weight&#44; height&#44; and categorizing BMI&#46; As a result&#44; both groups had the same risk of mortality at the ICU setting&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">To reduce clinical heterogeneity&#44; a second sensitivity analysis was conducted and the prospective studies that analyzed the low-body-weight subgroup &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>18&#46;5<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; were excluded since evidence shows that this subgroup has higher mortality rates&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">29</span></a> As in the aforementioned analysis&#44; the result showed no differences regarding mortality between obese and nonobese patients receiving IMV in the ICU setting&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">As it is the case with other reviews<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">14&#44;17</span></a> the Newcastle-Ottawa scale<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">24</span></a> was the tool of choice to assess the quality of observational studies&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">14</span></a> However&#44; the lack of rigorous manuals makes the interpretation of this tool by the user a difficult task&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">38</span></a></p><p id="par0375" class="elsevierStylePara elsevierViewall">On the other hand&#44; the quality of evidence was assessed using the GRADE score<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">25</span></a> since it is mandatory for new reviews and is applied on nonrandomized trials such as those included in this review&#46; The 14 studies included were analyzed for the main result variable and the quality of evidence found was low&#46;</p><p id="par0380" class="elsevierStylePara elsevierViewall">The quality of evidence of time variables was not assessed using this scale since they were not meta-analyzed&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Limitations</span><p id="par0385" class="elsevierStylePara elsevierViewall">The subgroup comparison of normal-body-weight subjects &#40;BMI 18&#46;5&#8211;24&#46;99<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; versus obese subjects &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; was not possible because not all primary studies stratified it this way&#46; Also&#44; because the author we contacted over the e-mail did not get back to us&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall">We could not conduct a meta-regression analysis to assess how mortality behaves in both groups&#46; Also&#44; we did not assess the influence of the variables that may be confounding factors such as age&#44; underlying conditions&#44; reason for IMV or severity of patients at the ICU admission&#46; The problem here was that not all studies described these data and those that described them did it in a different way&#46;</p><p id="par0395" class="elsevierStylePara elsevierViewall">Regarding the tool used to assess the study methodological quality&#44; no recommendation advocates for its reliability or validity&#46; It does not stratify studies based on methodological quality either&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Conclusion</span><p id="par0400" class="elsevierStylePara elsevierViewall">This SR found no correlation between the subgroup of obese adult patients who received IMV and mortality at the ICU setting&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall">The studies included did not allow us to analyze the demographic and time variables because of the different ways the authors expressed such variables and the low quality of evidence available&#46;</p><p id="par0410" class="elsevierStylePara elsevierViewall">We believe it is essential to achieve consensus in future studies to have a more operative registry of such variables so that the conclusions drawn can be more solid&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Conflict of interest</span><p id="par0415" class="elsevierStylePara elsevierViewall">None of the aforementioned authors declared any conflicts of interest whatsoever&#46;</p></span></span>"
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          "titulo" => "Acknowledgements"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-02-23"
    "fechaAceptado" => "2018-07-09"
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          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:5 [
            0 => "Obesity"
            1 => "Mortality"
            2 => "Artificial respiration"
            3 => "Intensive Care Units"
            4 => "Meta-analysis"
          ]
        ]
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            0 => "Obesidad"
            1 => "Mortalidad"
            2 => "Respiraci&#243;n artificial"
            3 => "Unidad de cuidados intensivos"
            4 => "Metaan&#225;lisis"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate if there is an association between obesity and mortality in the Intensive Care Unit &#40;ICU&#41; in adult patients receiving invasive mechanical ventilation&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Systematic review with meta-analysis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Scope</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">ICU&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Data source</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A search was made in MEDLINE&#44; Cochrane Library&#44; CINAHL and Global Health databases without language restriction&#44; until February 21&#44; 2017&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Selection of studies</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Studies that reported mortality in the ICU in obese versus non-obese patients who received IMV were included&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Main variables</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Mortality in the ICU&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">2163 articles were found&#44; of which 14 studies were included&#46; No statistically significant differences were found between obese and non-obese patients with respect to the variable mortality in the ICU &#40;OR&#58; 0&#46;94&#44; 95&#37; CI&#58; 0&#46;81&#8211;1&#46;10&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;45&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">No relationship was found between the subgroup of obese adult patients receiving IMV and the mortality variable in the ICU&#46;</p></span>"
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            "titulo" => "Design"
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            "titulo" => "Scope"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Evaluar si existe asociaci&#243;n entre obesidad y mortalidad en la Unidad de Cuidados Intensivos &#40;UCI&#41; en pacientes adultos que reciben ventilaci&#243;n mec&#225;nica invasiva&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Dise&#241;o</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Revisi&#243;n sistem&#225;tica con metaan&#225;lisis&#46;</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">&#193;mbito</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">UCI&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Fuente de datos</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; una b&#250;squeda en las bases de datos MEDLINE&#44; Cochrane Library&#44; CINAHL y Global Health sin restricci&#243;n de lenguaje&#44; hasta el 21 de febrero del a&#241;o 2017&#46;</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Selecci&#243;n de estudios</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron estudios que informaron mortalidad en UCI en pacientes obesos versus no obesos que recibieron VMI&#46;</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Variables principal</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Mortalidad en UCI&#46;</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Se hallaron 2&#46;163 art&#237;culos&#44; de los cuales se incluyeron 14 estudios&#46; No se encontraron diferencias estad&#237;sticamente significativas entre los pacientes obesos y no obesos respecto a la variable mortalidad en UCI <span class="elsevierStyleItalic">&#40;odds ratio</span>&#58; 0&#44;94&#59; intervalo de confianza del 95&#37;&#58; 0&#44;81-1&#44;10&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;45&#41;&#46;</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusi&#243;n</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">No se hall&#243; relaci&#243;n entre el subgrupo de pacientes adultos obesos que reciben VMI y la variable mortalidad en UCI&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Tocalini P&#44; Vicente A&#44; Amoza RL&#44; Garc&#237;a Reid C&#44; Cura AJ&#44; Tozzi WA&#44; et al&#46; Asociaci&#243;n entre obesidad y mortalidad en pacientes adultos que reciben ventilaci&#243;n mec&#225;nica invasiva&#58; una revisi&#243;n sistem&#225;tica y metaan&#225;lisis&#46; Med Intensiva&#46; 2020&#59;44&#58;18&#8211;26&#46;</p>"
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            "titulo" => "Supplementary data"
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Flow chart&#46;</p>"
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          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Forest plot of all the studies included regarding the mortality variable at the ICU setting&#46; BMI&#44; body mass index&#46;</p>"
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        "etiqueta" => "Figure 3"
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          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Forest plot of the mortality variable at the ICU setting of all prospective studies&#46;</p>"
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          "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Forest plot of the mortality variable at the ICU setting of all retrospective studies&#46;</p>"
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          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Forest plot of the mortality variable at the ICU setting of prospective studies without the subgroup of low-body-weight patients &#40;MBI 18&#46;5&#8211;29&#46;9<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46;</p>"
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          "en" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Funnel plot for the assessment of publication bias&#46; The line which is dotted represents the composite outcomes of all studies&#46; SE &#40;log OR&#41;&#59; SE&#44; standard error&#59; OD&#44; odds ratio based on the randomized model&#46;</p>"
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      "titulo" => "References"
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Article information

ISSN: 21735727
Original language: English

DOI:10.1016/j.medine.2019.11.002

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Year/Month	Html	Pdf	Total

2024 November	5	2	7
2024 October	49	34	83
2024 September	74	59	133
2024 August	60	49	109
2024 July	47	44	91
2024 June	95	47	142
2024 May	74	48	122
2024 April	41	27	68
2024 March	55	30	85
2024 February	45	37	82
2024 January	30	42	72
2023 December	29	33	62
2023 November	50	40	90
2023 October	33	32	65
2023 September	32	30	62
2023 August	33	18	51
2023 July	39	33	72
2023 June	39	23	62
2023 May	59	53	112
2023 April	63	27	90
2023 March	77	27	104
2023 February	64	34	98
2023 January	52	46	98
2022 December	82	45	127
2022 November	74	36	110
2022 October	77	62	139
2022 September	48	34	82
2022 August	60	51	111
2022 July	47	55	102
2022 June	34	24	58
2022 May	49	37	86
2022 April	63	42	105
2022 March	55	52	107
2022 February	51	31	82
2022 January	72	35	107
2021 December	49	50	99
2021 November	55	43	98
2021 October	76	96	172
2021 September	45	43	88
2021 August	40	42	82
2021 July	39	36	75
2021 June	43	31	74
2021 May	60	58	118
2021 April	206	103	309
2021 March	183	48	231
2021 February	96	48	144
2021 January	93	33	126
2020 December	99	34	133
2020 November	61	22	83
2020 October	22	9	31
2020 July	30	16	46
2020 June	24	18	42
2020 May	49	14	63
2020 April	24	19	43
2020 March	1	0	1
2020 February	1	0	1

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