<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OJEM</journal-id><journal-title-group><journal-title>Open Journal of Emergency Medicine</journal-title></journal-title-group><issn pub-type="epub">2332-1806</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/ojem.2016.44011</article-id><article-id pub-id-type="publisher-id">OJEM-71836</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Diagnostic Accuracy of Transthoracic Echocardiography to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill: A Meta-Analysis
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Xiang</surname><given-names>Si</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Daiyin</surname><given-names>Cao</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Jianfeng</surname><given-names>Wu</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Juan</surname><given-names>Chen</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Zimeng</surname><given-names>Liu</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Minying</surname><given-names>Chen</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bin</surname><given-names>Ouyang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Xiangdong</surname><given-names>Guan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff2"><addr-line>Department of Critical Care Medicine, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China</addr-line></aff><aff id="aff1"><addr-line>Department of Surgical Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China</addr-line></aff><author-notes><corresp id="cor1">* E-mail:<email>james_sixiang@163.com(XS)</email>;</corresp></author-notes><pub-date pub-type="epub"><day>08</day><month>11</month><year>2016</year></pub-date><volume>04</volume><issue>04</issue><fpage>83</fpage><lpage>92</lpage><history><date date-type="received"><day>October</day>	<month>11,</month>	<year>2016</year></date><date date-type="rev-recd"><day>Accepted:</day>	<month>November</month>	<year>5,</year>	</date><date date-type="accepted"><day>November</day>	<month>8,</month>	<year>2016</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Background: Hemodynamic instability is common in critical patients and not all patients respond to fluid challenge, so we need accurate and rapid hemodynamic techniques to help the clinicians to guide fluid treatment. Numerous hemodynamic techniques have been used to predict fluid responsiveness till now. Transthoracic echocardiography (TTE) appears to have the ability to predict fluid responsiveness, but there is no consensus on whether it can be used by passive leg raising (PLR). Methods: We performed a literature search using MEDLINE (source PubMed, from 1947), EMBASE (from 1974) and the Cochrane Database of Systematic Reviews for prospective studies with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Results: 7 prospective studies involving 261 patients and 285 boluses were identified. The pooled sensitivity and specificity of TTE are 86% (79% - 91%) and 90% (83% - 94%), respectively. The summary receiver operating characteristic (sROC) curve shows an optimum joint sensitivity and specificity of 0.88, with area under the sROC curve (AUC) of 0.94. The result of diagnostic odds ratio (DOR) is 50.62 (95% confidence interval [CI]: 23.70 - 108.12). The results of positive likelihood ratio (+LR) and negative likelihood ratio (?LR) are 7.07 (95% CI: 4.39 - 11.38) and 0.19 (95% CI: 0.13 - 0.28), which indicated strong diagnostic evidence. Conclusions: TTE is a repeatable and reliable noninvasive tool to predict fluid responsiveness in the critically ill during PLR with good test performance. This meta-analysis brings evidence to employ well-trained clinician-echocardiographers to assess patients’ volume statue via TTE to benefit daily work in intensive care units (ICUs). 
 
</p></abstract><kwd-group><kwd>TTE</kwd><kwd> PLR</kwd><kwd> Fluid Responsiveness</kwd><kwd> Meta-Analysis</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>The management of the critically ill patient to optimization the tissue oxygen delivery is an essential part in intensive care unit (ICU). Insufficient intravascular loading in the early resuscitation of acute sepsis results in tissue under perfusion, organ dysfunction, and acidosis. Excessive fluid administration has also been shown to be detrimental in the perioperative setting and in acute lung injury, prolonging both time on mechanical ventilation and time in intensive care [<xref ref-type="bibr" rid="scirp.71836-ref1">1</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref2">2</xref>] . However, it has been reported 50 percent of patients do not exhibit the desired effect after fluid bolus [<xref ref-type="bibr" rid="scirp.71836-ref3">3</xref>] and more than half of patients have the risk of excessive fluid administration [<xref ref-type="bibr" rid="scirp.71836-ref4">4</xref>] . It is therefore essential to have reliable tools for predicting the efficacy of volume expansion (VE) and thus distinguishing patients who might benefit from VE from those in whom the treatment is likely to be inefficacious.</p><p>For the past 10 years, many studies have focused on the prediction of fluid responsiveness. Static hemodynamic indices (such as central venous pressure [CVP] or pulmonary artery occlution pressure [PAOP]) are demonstrated to be little value in predicting fluid responsiveness [<xref ref-type="bibr" rid="scirp.71836-ref5">5</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref6">6</xref>] . Dynamic indices (such as stroke volume variation [SVV] or pulse pressure variation [PPV]), based on analysis of preload dependence, have been validated to predict fluid responsiveness [<xref ref-type="bibr" rid="scirp.71836-ref5">5</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref7">7</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref8">8</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref9">9</xref>] . And now modern intensive care is increasingly concerned with the avoidance of unnecessary invasive procedures which contribute to patient morbidity either directly or more often through the associated risk of catheter-related bloodstream infection [<xref ref-type="bibr" rid="scirp.71836-ref10">10</xref>] . So, invasive or mini- invasive methods are replacing by new methods focused on non-invasive.</p><p>Passive leg raising (PLR) is a reversible maneuver that mimics VE by shifting venous blood from the lower limbs toward the intrathoracic compartment [<xref ref-type="bibr" rid="scirp.71836-ref11">11</xref>] . This provides a transient volume load of between 150 and 300 milliliters to the central circulation in one minute [<xref ref-type="bibr" rid="scirp.71836-ref12">12</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref13">13</xref>] . Because the heart (left and right ventricles) works on the stiff portion of the Frank-Starling relationship, therefore PLR can increase cardiac preload as “auto-transfused” into the central circulation [<xref ref-type="bibr" rid="scirp.71836-ref11">11</xref>] . Transthoracic echocardiography (TTE) is increasingly used for noninvasive hemodynamic assessment of critically ill patients since high-quality images and Doppler signals are obtained with recent TTE equipment [<xref ref-type="bibr" rid="scirp.71836-ref14">14</xref>] . TTE provides clinicians with valuable information including stroke volume, left ventricular preload, and filling. The stroke volume can be easily obtained using the left ventricular outflow track Doppler method [<xref ref-type="bibr" rid="scirp.71836-ref21">21</xref>] . But there is no consensus on whether it is useful during passive leg raising. Accordingly, the aim of this study is to answer the question: Can transthoracic echocardiography to be used as a tool for predicting volume responsiveness in critically ill by PLR?</p></sec><sec id="s2"><title>2. Methods</title><sec id="s2_1"><title>2.1. Study Selection</title><p>Two authors independently performed a search in MEDLINE (using PubMed as the search engine, from 1947), EMBASE (from 1974) and the Cochrane Database of Systematic Reviews for prospective studies with the following key words: ((transthoracic OR thoracic) AND (echocardiograph* OR echog* OR doppler)) AND “passive leg raising”.</p><p>Only full-text articles in indexed journals were included. Reviews, chapter, case reports, reference network and studies published in abstract form were excluded. No language restriction was imposed. We included only studies with adult patients admitted in ICU. Articles were collected by one reviewer and crosschecked by another reviewer and references of included papers were examined to identify other studies of interest.</p></sec><sec id="s2_2"><title>2.2. Inclusion Criteria</title><p>We included full-text studies with the following criteria: 1) PLR was performed and followed with VE; 2) the number of patients and boluses had been counted; 3) the reference standard of predicting fluid responsiveness had been described; 4) sensitivity, specificity and the threshold of the index in identifying those patients who subsequently responded to VE had been calculated.</p></sec><sec id="s2_3"><title>2.3. Data Extraction and Quality Assessment</title><p>Data extraction of all variables and outcomes of interest was performed independently by 2 authors independently. For all included studies, two authors extracted the following information by using a standardized form: authors, year of publication, study setting, population, age of patients, number of patients included, ventilation mode, cardiac rhythm (sinus vs. arrhythmias), type and amount of VE, time of VE, definition of responders, position, manufacturer of TTE, amount of VE administered, number and percentage of responders, sensitivity, specificity, best threshold and area under the ROC curve (AUC). Data reporting conformed to the Standards for Reporting of Diagnostic Accuracy (STARD) [<xref ref-type="bibr" rid="scirp.71836-ref15">15</xref>] .</p><p>We use QUADAS-2 (quality assessment of diagnostic accuracy-2) [<xref ref-type="bibr" rid="scirp.71836-ref16">16</xref>] to assess the quality of included studies on diagnostic accuracy in systematic reviews. The checklist was structured with 4 parts: Patient selection, index test, reference standard and flow and timing.</p></sec><sec id="s2_4"><title>2.4. Statistical Analysis</title><p>We used RevMan 5.2 (Cochrane Collaboration, Oxford, UK) to make the QUADAS-2 scale to assess quality of studies on diagnostic accuracy to be included in systematic reviews [<xref ref-type="bibr" rid="scirp.71836-ref17">17</xref>] . Using MetaDiSC 1.4 (Unit of Clinical Biostatistics team of the Ramon y Cajal Hospital, Madrid, Spain), we calculated pooled values of sensitivity, specificity, diagnostic odds ratio (DOR) and area under summary receiver operating characteristic (sROC) curve with P-values of less than 0.05 considered statistically significant [<xref ref-type="bibr" rid="scirp.71836-ref18">18</xref>] . Pubilication bias was performed by STATA statistical software 12.0 (StataCorp, College Station, TX) [<xref ref-type="bibr" rid="scirp.71836-ref19">19</xref>] .</p></sec></sec><sec id="s3"><title>3. Results</title><sec id="s3_1"><title>3.1. Article Search</title><p>The initial search yielded 345 articles, of which 93 articles were excluded for not directly concerning of this item. 122 articles were subsequently excluded for review, reference work and book. Based on the inclusion criteria, 65 articles were excluded. 58 articles were subsequently excluded for not using TTE. Finally, 7 full-text articles were included for meta-analysis [<xref ref-type="bibr" rid="scirp.71836-ref20">20</xref>] - [<xref ref-type="bibr" rid="scirp.71836-ref26">26</xref>] .</p></sec><sec id="s3_2"><title>3.2. Quality of Reporting and Study Characteristics</title><p>Characteristics of the 7 included articles are summarized in <xref ref-type="table" rid="table1">Table 1</xref> and the main results are reported in <xref ref-type="table" rid="table2">Table 2</xref>. The results of QUADAS-2 are showed in <xref ref-type="fig" rid="fig1">Figure 1</xref>.</p><p>All the included 7 studies (261 patients, 285 boluses) were prospective studies with critically ill patients in shock. 3 studies [<xref ref-type="bibr" rid="scirp.71836-ref21">21</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref23">23</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref24">24</xref>] enrolled patients with spontaneous breathing and in sinus rhythm. The others enrolled patients adapted to ventilator and in rhythm or arrhythmia. 2 studies [<xref ref-type="bibr" rid="scirp.71836-ref22">22</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref26">26</xref>] took transthoracic Doppler ultrasound device (USCOM&#174;) for hemodynamic monitoring and traditional transthoracic echocardiography was used by the other studies. In all, 261 patients (range 17 - 89 for single paper) enrolled. A total of 285 fluid boluses were administered. The mean responder rate was 53.9%.</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Characteristics of studies included in this meta-analysis</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Authors</th><th align="center" valign="middle" >Year</th><th align="center" valign="middle" >NO.</th><th align="center" valign="middle" >Ventilation</th><th align="center" valign="middle" >Rhythm</th><th align="center" valign="middle" >VE</th><th align="center" valign="middle" >Time</th><th align="center" valign="middle" >Position</th><th align="center" valign="middle" >Responder</th><th align="center" valign="middle" >Index</th><th align="center" valign="middle" >Device</th></tr></thead><tr><td align="center" valign="middle" >Lamia [<xref ref-type="bibr" rid="scirp.71836-ref20">20</xref>]</td><td align="center" valign="middle" >2007</td><td align="center" valign="middle" >24</td><td align="center" valign="middle" >MV/SB</td><td align="center" valign="middle" >sinus/AF</td><td align="center" valign="middle" >500cc saline</td><td align="center" valign="middle" >over 15 min</td><td align="center" valign="middle" >semirecumbent position</td><td align="center" valign="middle" >△SVI ≥ 15%</td><td align="center" valign="middle" >cVTIAo</td><td align="center" valign="middle" >TTE (Philips)</td></tr><tr><td align="center" valign="middle" >Maizel [<xref ref-type="bibr" rid="scirp.71836-ref21">21</xref>]</td><td align="center" valign="middle" >2007</td><td align="center" valign="middle" >34</td><td align="center" valign="middle" >SB</td><td align="center" valign="middle" >sinus</td><td align="center" valign="middle" >500cc saline</td><td align="center" valign="middle" >over 15 min</td><td align="center" valign="middle" >supine position</td><td align="center" valign="middle" >△CO ≥ 12%</td><td align="center" valign="middle" >cCO cSV</td><td align="center" valign="middle" >TTE (Philips)</td></tr><tr><td align="center" valign="middle" >Thiel [<xref ref-type="bibr" rid="scirp.71836-ref22">22</xref>]</td><td align="center" valign="middle" >2009</td><td align="center" valign="middle" >89</td><td align="center" valign="middle" >MV/SB</td><td align="center" valign="middle" >sinus/arr</td><td align="center" valign="middle" >500cc saline Ringer’s lactate hetastarch</td><td align="center" valign="middle" >-</td><td align="center" valign="middle" >semi-recumbent position</td><td align="center" valign="middle" >△SV ≥ 15%</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >TTE (USCOM&#174;)</td></tr><tr><td align="center" valign="middle" >Biais [<xref ref-type="bibr" rid="scirp.71836-ref23">23</xref>]</td><td align="center" valign="middle" >2009</td><td align="center" valign="middle" >30</td><td align="center" valign="middle" >SB</td><td align="center" valign="middle" >sinus</td><td align="center" valign="middle" >500cc saline</td><td align="center" valign="middle" >15 min</td><td align="center" valign="middle" >semi-recumbent position</td><td align="center" valign="middle" >△SV ≥ 15%</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >TTE (Siemens)</td></tr><tr><td align="center" valign="middle" >Pr&#233;au [<xref ref-type="bibr" rid="scirp.71836-ref24">24</xref>]</td><td align="center" valign="middle" >2010</td><td align="center" valign="middle" >34</td><td align="center" valign="middle" >SB</td><td align="center" valign="middle" >sinus</td><td align="center" valign="middle" >500cc HES</td><td align="center" valign="middle" >over 30 min</td><td align="center" valign="middle" >semi-recumbent position</td><td align="center" valign="middle" >△SV ≥ 15%</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >TTE (Philips)</td></tr><tr><td align="center" valign="middle" >Guinot [<xref ref-type="bibr" rid="scirp.71836-ref25">25</xref>]</td><td align="center" valign="middle" >2011</td><td align="center" valign="middle" >17</td><td align="center" valign="middle" >MV</td><td align="center" valign="middle" >sinus/arr</td><td align="center" valign="middle" >500cc saline</td><td align="center" valign="middle" >15 min</td><td align="center" valign="middle" >semi-recumbent position</td><td align="center" valign="middle" >△SV &gt; 15%</td><td align="center" valign="middle" >cSV cCO</td><td align="center" valign="middle" >TTE (Philips)</td></tr><tr><td align="center" valign="middle" >Wang [<xref ref-type="bibr" rid="scirp.71836-ref26">26</xref>]</td><td align="center" valign="middle" >2011</td><td align="center" valign="middle" >33</td><td align="center" valign="middle" >MV/SB</td><td align="center" valign="middle" >sinus/arr</td><td align="center" valign="middle" >500cc saline</td><td align="center" valign="middle" >15 min</td><td align="center" valign="middle" >semi-recumbent position</td><td align="center" valign="middle" >△SV ≥ 15%</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >TTE (USCOM&#174;)</td></tr></tbody></table></table-wrap><p>MV, mechanical ventilation, arr, arrhythmia, AF, atrial fibrillation, VE, volume expansion, min, minutes, Δ, variation; c PLR induced changes in, CO, cardiac output, SV, stroke volume, VTIAo, aortic velocity-time integral, SVI, stroke volume index, TTE, transthoracic echocardiography, USCOM, transthoracic Doppler ultrasonography.</p><table-wrap id="table2" ><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> Main results of studies included in this meta-analysis on TTE in predicting fluid responsiveness by PLR</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Authors</th><th align="center" valign="middle" >Index</th><th align="center" valign="middle" >Boluses</th><th align="center" valign="middle" >Rps %</th><th align="center" valign="middle" >AUC</th><th align="center" valign="middle" >Best threshold</th><th align="center" valign="middle" >r</th><th align="center" valign="middle" >Sens.</th><th align="center" valign="middle" >Spec.</th><th align="center" valign="middle" >DOR</th><th align="center" valign="middle" >+LR</th><th align="center" valign="middle" >−LR</th></tr></thead><tr><td align="center" valign="middle" >Lamia [<xref ref-type="bibr" rid="scirp.71836-ref20">20</xref>]</td><td align="center" valign="middle" >cVTIAo</td><td align="center" valign="middle" >24</td><td align="center" valign="middle" >54</td><td align="center" valign="middle" >0.96</td><td align="center" valign="middle" >12.5</td><td align="center" valign="middle" >0.83</td><td align="center" valign="middle" >77</td><td align="center" valign="middle" >100</td><td align="center" valign="middle" >69</td><td align="center" valign="middle" >18</td><td align="center" valign="middle" >0.3</td></tr><tr><td align="center" valign="middle" >Maizel [<xref ref-type="bibr" rid="scirp.71836-ref21">21</xref>]</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >34</td><td align="center" valign="middle" >50</td><td align="center" valign="middle" >0.9</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" ></td><td align="center" valign="middle" >88</td><td align="center" valign="middle" >83</td><td align="center" valign="middle" >35</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >0.1</td></tr><tr><td align="center" valign="middle" >Thiel [<xref ref-type="bibr" rid="scirp.71836-ref22">22</xref>]</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >102</td><td align="center" valign="middle" >46</td><td align="center" valign="middle" >0.89</td><td align="center" valign="middle" >15</td><td align="center" valign="middle" ></td><td align="center" valign="middle" >81</td><td align="center" valign="middle" >93</td><td align="center" valign="middle" >54</td><td align="center" valign="middle" >11</td><td align="center" valign="middle" >0.2</td></tr><tr><td align="center" valign="middle" >Biais [<xref ref-type="bibr" rid="scirp.71836-ref23">23</xref>]</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >30</td><td align="center" valign="middle" >67</td><td align="center" valign="middle" >0.92</td><td align="center" valign="middle" >16</td><td align="center" valign="middle" ></td><td align="center" valign="middle" >85</td><td align="center" valign="middle" >90</td><td align="center" valign="middle" >51</td><td align="center" valign="middle" >9</td><td align="center" valign="middle" >0.2</td></tr><tr><td align="center" valign="middle" >Pr&#233;au [<xref ref-type="bibr" rid="scirp.71836-ref24">24</xref>]</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >34</td><td align="center" valign="middle" >41</td><td align="center" valign="middle" >0.94</td><td align="center" valign="middle" >10</td><td align="center" valign="middle" >0.86</td><td align="center" valign="middle" >86</td><td align="center" valign="middle" >90</td><td align="center" valign="middle" >54</td><td align="center" valign="middle" >9</td><td align="center" valign="middle" >0.2</td></tr><tr><td align="center" valign="middle" >Guinot [<xref ref-type="bibr" rid="scirp.71836-ref25">25</xref>]</td><td align="center" valign="middle" >cCO</td><td align="center" valign="middle" >25</td><td align="center" valign="middle" >52</td><td align="center" valign="middle" >0.87</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >0.84</td><td align="center" valign="middle" >85</td><td align="center" valign="middle" >83</td><td align="center" valign="middle" >28</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >0.2</td></tr><tr><td align="center" valign="middle" >Wang [<xref ref-type="bibr" rid="scirp.71836-ref26">26</xref>]</td><td align="center" valign="middle" >cSV</td><td align="center" valign="middle" >36</td><td align="center" valign="middle" >67</td><td align="center" valign="middle" >0.95</td><td align="center" valign="middle" >15</td><td align="center" valign="middle" ></td><td align="center" valign="middle" >100</td><td align="center" valign="middle" >83.3</td><td align="center" valign="middle" >206</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >0</td></tr><tr><td align="center" valign="middle" >Overall (95% CIs)</td><td align="center" valign="middle" ></td><td align="center" valign="middle" >285</td><td align="center" valign="middle" >53.857</td><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" >85.8</td><td align="center" valign="middle" >89.8</td><td align="center" valign="middle" >50.6</td><td align="center" valign="middle" >7.1</td><td align="center" valign="middle" >0.19</td></tr><tr><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" ></td><td align="center" valign="middle" >(79.1 - 91.0)</td><td align="center" valign="middle" >(83.4 - 94.3)</td><td align="center" valign="middle" >(23.7 - 108.1)</td><td align="center" valign="middle" >(4.4 - 11.4)</td><td align="center" valign="middle" >(0.13 - 0.28)</td></tr></tbody></table></table-wrap><p>AUC, area under the receiver operating characteristics curve, c PLR induced changes in, Rps, responders, 95% CIs, 95% confidence intervals, Sens, sensitivity, Spec, specificity, DOR, diagnostic odds ratio, +LR, positive likelihood ratio, −LR, negative likelihood ratio, SV, stroke volume, CO, cardiac output, VTIAo, aortic velocity-time integral.</p><fig id="fig1"  position="float"><label><xref ref-type="fig" rid="fig1">Figure 1</xref></label><caption><title> QUADAS-2 results of included studies on TTE in predicting fluid responsiveness by PLR (software RevMan 5.2)</title></caption><graphic mimetype="image"   position="float"  xlink:type="simple"  xlink:href="http://html.scirp.org/file/1-1750056x2.png"/></fig></sec><sec id="s3_3"><title>3.3. Diagnostic Accuracy</title><p>Forest plots of the pooled sensitivity and specificity are shown in <xref ref-type="fig" rid="fig2">Figure 2</xref>.</p><p>The results I2 = 0.0% (&lt;50%) and p = 0.972 (&gt;0.05) showed that heterogeneity was not significant among the trials. The sensitivity ranged from 77% - 100% (pooled sensitivity 86%, 95% CI: 79% - 91%), while specificity ranged from 82% - 100% (pooled specificity 90%, 95% CI: 83% - 94%). The +LR was 7.07 (95% CI: 4.39 - 11.38), −LR was 0.19 (95% CI: 0.13 - 0.28), and DOR was 50.62 (95% CI: 23.70 - 108.12). Chi-square values for sensitivity, specificity, +LR, −LR, and DOR were 9.06 (P = 0.17), 4.74 (P = 0.578), 2.53 (P = 0.865), 3.14 (P = 0.792), and 1.29 (P = 0.972), respectively. These also indicated heterogeneity was not significant across studies regarding sensitivity, specificity, +LR, −LR, and DOR.</p><p>As shown in <xref ref-type="fig" rid="fig3">Figure 3</xref>, the sROC curve showing sensitivity versus 1-specificity from individual studies is not positioned near the desirable upper left corner. The maximum joint sensitivity and specificity was 0.88, with AUC of 0.94.</p><fig id="fig2"  position="float"><label><xref ref-type="fig" rid="fig2">Figure 2</xref></label><caption><title> Forest Plots of Pooled Sensitivity and specificity of the included studieson TTE in predicting fluid respon-siveness by PLR</title></caption><graphic mimetype="image"   position="float"  xlink:type="simple"  xlink:href="http://html.scirp.org/file/1-1750056x3.png"/></fig><fig id="fig3"  position="float"><label><xref ref-type="fig" rid="fig3">Figure 3</xref></label><caption><title> Summary Receiver Operating Characteristics Curve for the ability of TTE in predicting fluid responsiveness by PLR</title></caption><graphic mimetype="image"   position="float"  xlink:type="simple"  xlink:href="http://html.scirp.org/file/1-1750056x4.png"/></fig><p>The Egger test and Begg test showed that the potential publication bias was significant (P &lt; 0.05), which indicated a potential for publication bias. Due to the limited number of included studies in the meta-analysis, funnel plots were not assessed.</p></sec></sec><sec id="s4"><title>4. Discussion</title><p>The results of the present meta-analysis demonstrate that the pooled sensitivity and specificity of TTE are 86% (79% - 91%) and 90% (83% - 94%), respectively. The sROC curve shows an optimum joint sensitivity and specificity of 0.88, with AUC of 0.94, which indicates that TTE is good tool to be used to predict fluid responsiveness. The result of DOR is 50.62 (95% CI: 23.70 - 108.12), which indicates using non-invasive techniques have better discriminatory test performance with higher DOR values [<xref ref-type="bibr" rid="scirp.71836-ref8">8</xref>] ; the results of +LR and −LR are 7.07 (95% CI: 4.39 - 11.38) and 0.19 (95% CI: 0.13 - 0.28). +LR above 5 and −LR below 0.2 have been noted as providing strong diagnostic evidence [<xref ref-type="bibr" rid="scirp.71836-ref27">27</xref>] .</p><p>Passive leg raising (PLR) is a reversible maneuver that mimics rapid VE by shifting venous blood from the lower limbs to the intrathoracic compartment and introduces a reversible increase in preload of the right [<xref ref-type="bibr" rid="scirp.71836-ref28">28</xref>] and left ventricle [<xref ref-type="bibr" rid="scirp.71836-ref29">29</xref>] . TTE is a safe and convenient hemodynamic tool, which enable clinicians make fast assessment of patients’ volume statue at the bedside, especially in patients with spontaneous breathing. In such patients, volume responsiveness is difficult to predict [<xref ref-type="bibr" rid="scirp.71836-ref30">30</xref>] [<xref ref-type="bibr" rid="scirp.71836-ref31">31</xref>] . TTE techniques appear useful in patients with spontaneous respiratory effort and those with arrhythmias: this is in contrast to many of the techniques that involve invasive monitoring which have been shown to be inaccurate in these situations [<xref ref-type="bibr" rid="scirp.71836-ref32">32</xref>] . But the operation of TTE really needs qualified clinicians. A good clinician can obtain the information from the TTE screen accurately.</p><p>A recent study by Mandeville et al. [<xref ref-type="bibr" rid="scirp.71836-ref33">33</xref>] concludes that TTE accurately predict fluid responsiveness in critically ill patients with discriminative power not affected by the technique selected. But the predictive value of TTE has not been evaluated yet. In this meta-analysis, it has been suggested that TTE could accurately predict fluid responsiveness by passive leg raising in the critically ill patients.</p><p>This meta-analysis has certain limitations. First, thoracic or abdominal wounds may sometimes make views impossible to achieve and obesity or rib prominence can also make TTE acoustic windows difficult to obtain. Second, TTE requires qualified clinician-echocardiographers through a defined training process, who can obtain information from the screen of TTE accurately and answer to the daily clinical conundrum of fluid responsiveness. Third, small size of the studies is included in this study with only a single study included 89 patients [<xref ref-type="bibr" rid="scirp.71836-ref20">20</xref>] . However, Zhang et al confirmed that small trials are more likely to report larger beneficial effects than large trials in critical care medicine, and Caution should be practiced in the interpretation of meta-analyses involving small trials [<xref ref-type="bibr" rid="scirp.71836-ref34">34</xref>] . Finally, the pooling of diagnostic accuracy data inevitably contribute to sources of bias [<xref ref-type="bibr" rid="scirp.71836-ref29">29</xref>] , which are revealed in the significant amount of statistical heterogeneity across studies. As positive results of studies are more likely to be published, publication bias may be introduced by inflation of diagnostic accuracy estimates.</p><p>TTE is a repeatable and reliable noninvasive tool to predict fluid responsiveness in the critically ill during PLR with good test performance. This meta-analysis gives evidence to bring up well-trained clinician-echocardiographers to assess patients’ volume statue via TTE to benefit daily work in ICUs.</p></sec><sec id="s5"><title>Financial Support and Sponsorship</title><p>This work was supported by the grants from the Fundamental Research Funds for the Central Universities (15ykpy14) and Sun Yat-sen University Clinical Research 5010 Program (2007015).</p></sec><sec id="s6"><title>Conflicts of Interest</title><p>There are no conflicts of interest.</p></sec><sec id="s7"><title>Cite this paper</title><p>Si, X., Cao, D.Y., Wu, J.F., Chen, J., Liu, Z.M., Chen, M.Y., Ouyang, B. and Guan, X.D. (2016) Diagnostic Accuracy of Transthoracic Echocardiography to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill: A Meta-Analysis. 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