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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.0" specific-use="sps-1.5" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">T4ypH7Mjcghdxm3zJQt3BhD</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2017000400297</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20170044</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
          <subj-group>
            <subject>Cardiac Surgery - Adults</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Comparison of Two Central Venous Pressure Control Strategies to Prevent Atrial Fibrillation After Coronary Artery Bypass Grafting</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Mario Augusto Cray da</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lirani</surname>
            <given-names>Wesley</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wippich</surname>
            <given-names>Ana Caroline</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Luana</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tolentino</surname>
            <given-names>Eduardo de Souza</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zampar</surname>
            <given-names>Beatriz</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Schafranski</surname>
            <given-names>Marcelo Derbli</given-names>
          </name>
          <xref ref-type="aff" rid="aff1"/>
        </contrib>
        <aff id="aff1">
          <institution content-type="orgname">Universidade Estadual de Ponta Grossa</institution>
          <addr-line>
            <named-content content-type="city">Ponta Grossa</named-content>
            <named-content content-type="state">PR</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Estadual de Ponta Grossa, Ponta Grossa, PR - Brazil</institution>
          <institution content-type="normalized">Universidade Estadual de Ponta Grossa</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Mario Augusto Cray da Costa</bold>, Rua Coronel Bittencourt, 567. Postal Code 84010-290, Centro, Ponta Grossa, PR - Brazil. E-mail: <email>drmarioaugusto@uol.com.br</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Costa MAC, Lirani W, Wippich AC, Schafranski MD; Acquisition of data, Analysis and interpretation of the data, Statistical analysis, Writing of the manuscript and Critical revision of the manuscript for intellectual contente: Costa MAC, Lirani W, Wippich AC, Lopes L, Tolentino ES, Zampar B, Schafranski MD; Obtaining financing: Costa MAC, Lirani W, Schafranski MD.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>04</month>
        <year>2017</year>
      </pub-date>
      <volume>108</volume>
      <issue>4</issue>
      <fpage>297</fpage>
      <lpage>303</lpage>
      <history>
        <date date-type="received">
          <day>26</day>
          <month>05</month>
          <year>2016</year>
        </date>
        <date date-type="rev-recd">
          <day>03</day>
          <month>06</month>
          <year>2016</year>
        </date>
        <date date-type="accepted">
          <day>01</day>
          <month>11</month>
          <year>2016</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Atrial fibrillation (AF) takes place in 10-40% of patients undergoing coronary artery bypass grafting (CABG), and increases cardiovascular mortality. Enlargement of atrial chambers is associated with increased AF incidence, so patients with higher central venous pressure (CVP) are expected to have larger atrial distension, which increases AF incidence.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To compare post-CABG AF incidence, following two CVP control strategies.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>Interventional, randomized, controlled clinical study. The sample comprised 140 patients undergoing CABG between 2011 and 2015. They were randomized into two groups, G15 and G20, with CVP maintained &#8804; 15 cmH<sub>2</sub>O and &#8804; 20 cmH<sub>2</sub>O, respectively.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>70 patients were included in each group. The AF incidence in G15 was 8.57%, and in G20, 22.86%, with absolute risk reduction of 14.28%, and number needed to treat (NNT) of 7 (p = 0.03). Mortality (G15 = 5.71%; G20 = 11.42%; p = 0.07), hospital length of stay (G15 = 7.14 days; G20 = 8.21 days; p = 0.36), number of grafts (median: G15 = 3, G2 = 2; p = 0.22) and cardiopulmonary bypass use (G15 = 67.10%; G20 = 55.70%; p = 0.22) were statistically similar. Age (p = 0.04) and hospital length of stay (p = 0.001) were significantly higher in patients who developed AF in both groups.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Keeping CVP low in the first 72 post-CABG hours reduces the relative risk of AF, and may be useful to prevent AF after CABG. </p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Central Venous Pressure</kwd>
        <kwd>Atrial Fibrillation/prevention</kwd>
        <kwd>Myocardial Revascularization</kwd>
        <kwd>Postoperative Care</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Atrial fibrillation (AF) is an arrhythmia that results from abnormal depolarization, causing loss of the atrial contraction ability. It is related to increased risk for stroke and mortality.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>Atrial fibrillation in the postoperative period (PO) of coronary artery bypass grafting (CABG) occurs in 5-40% of patients, usually from the second to the fourth PO day, peaking on the second day.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> Its pathophysiology is multifactorial and includes oxidative stress, systemic inflammatory response, excessive production of catecholamines, changes in autonomic tone and connexin expression. Such factors cause dispersion of atrial refractoriness, alter atrial electrical conduction and predispose to arrhythmia.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>The following risk factors are related to the higher incidence of post-CABG AF: advanced age, peripheral vascular disease, chronic obstructive pulmonary disease (COPD), diabetes mellitus, systemic arterial hypertension, valvular heart disease, left atrial enlargement, left ventricular dysfunction, history of previous AF or acute myocardial infarction (AMI), suspension of beta-blockers in the preoperative period, use of cardiopulmonary bypass (CPB), and increased PO sympathetic tone.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref>
			</p>
      <p>Atrial fibrillation in the PO period of CABG worsens the patient's hemodynamic status, because of the increased risk for congestive heart failure and embolic events in the long run. Stroke is a major complication, observed in 2% of surgical patients. In addition, AF has been associated with higher in-hospital mortality and worse survival in the long run.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> Such complications justify the need for prophylactic measures for post-CABG AF.</p>
      <p>The rationale of this study is based on the following hypothesis: the increased volume of the atria is associated with increased AF incidence;<xref ref-type="bibr" rid="B8">8</xref> therefore, patients with higher central venous pressure (CVP) are expected to have greater atrial distension, and, thus, a higher AF incidence, in addition to being predisposed to pulmonary congestion, hypoxemia and atrial wall edema, factors that contribute to increase the incidence of that arrhythmia. Thus, CVP control could be useful to prevent post-CABG AF. Aiming at testing that hypothesis, the post-CABG AF incidence was assessed under two CVP control strategies.</p>
    </sec>
    <sec>
      <title>Objective</title>
      <p>This study aimed at assessing whether the incidence of AF 48 to 72 hours after CABG differs between two CVP control strategies (based on intent to treat), by comparing two groups: G15 (CVP &#8804; 15 cmH<sub>2</sub>O) and G20 (CVP &#8804; 20 cmH<sub>2</sub>O), AF being the primary outcome. The secondary outcome was to compare hospital length of stay after CABG, as well as mortality, between both groups.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Type of study</title>
        <p>This is a clinical, randomized, controlled, interventional and prospective study performed at the Intensive Care Unit (ICU) of Santa Casa de Miseric&#243;rdia of Ponta Grossa, Paran&#225; State, in partnership with the State University of Ponta Grossa (UEPG). The analysis was performed with data prospectively collected. This study project was approved by the Ethics Committee in Research UEPG, abides by the 1975 Declaration of Helsinki, and all participants provided written informed consent before surgery.</p>
      </sec>
      <sec>
        <title>Inclusion and exclusion criteria</title>
        <p>This study sample comprised patients undergoing CABG at the Cardiac Surgery Service of the Santa Casa de Miseric&#243;rdia of Ponta Grossa from January 2011 to December 2015.</p>
        <p>Patients with the following characteristics were excluded: undergoing CABG in association with another procedure; history of preoperative AF; contraindication to maintain CVP below the established values (such as severe pulmonary hypertension); severe chronic renal failure, determined by a glomerular filtration rate &lt; 30 mL/min; severe left ventricular dysfunction; use of high doses of vasoactive drugs, such as dopamine or dobutamine &gt; 7mcg/kg/min or noradrenaline &gt; 0.7mcg/kg/min; no use of beta-blocker or statin in the preoperative period, or no diet reintroduction, and after vasoactive drug suspension in the PO period; need for more than 20 ampoules of furosemide within 24 hours to maintain CVP levels.</p>
      </sec>
      <sec>
        <title>Outcomes</title>
        <p><bold>Primary outcome:</bold> presence of AF 48 to 72 hours after CABG, on continuous electrocardiographic monitoring (cardioscope) and documented on 12-lead electrocardiogram (ECG).</p>
        <p><bold>Secondary outcomes:</bold> in-hospital mortality and hospital length of stay after CABG.</p>
      </sec>
      <sec>
        <title>Definition of the groups and data collection</title>
        <p>Patients were randomized into two groups by use of draw: G15, with a CVP goal of &#8804; 15 cmH<sub>2</sub>O; and G20, with a CVP goal of &#8804; 20 cmH<sub>2</sub>O. The strategy of CVP control consisted of measuring CVP every 2 hours for 72 hours after CABG, or until discharge from the ICU. The minimum ICU length of stay was 48 hours. Whenever CVP reached its cutoff point, a furosemide ampoule was intravenously administered, from the sixth hour on, because, in the first 6 post-CABG hours, hemodynamic instability is higher. Vasoactive or anti-hypertensive drugs were administered to maintain a mean arterial pressure (MAP) of 60-100 mm Hg. The AF incidence was compared between the groups, detected by use of continuous electrocardiographic monitoring (cardioscope) and confirmed on 12-lead ECG.</p>
        <p>The following data were collected daily: CVP levels, need for furosemide, AF occurrence within the post-CABG period (48 to 72 hours), hospital length of stay and in-hospital death.<xref ref-type="bibr" rid="B9">9</xref> The following surgical data and comorbidities were collected from the patients' standard preoperative and PO forms: age, sex, previous AF, diabetes mellitus, COPD, chronic kidney disease, peripheral vascular disease, left ventricular function, recent AMI, use of CPB, and number of grafts.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>The statistical analysis was performed in two steps. In the first, the following variables were compared between the G15 and G20 groups: age, sex, diabetes mellitus, COPD, peripheral arterial disease, recent AMI within three months from surgery, moderate left ventricular dysfunction (ejection fraction &lt; 50% and &gt; 35%), glomerular filtration rate, AF incidence, in-hospital death, post-CABG hospital length of stay (days), number of grafts, and use of CPB. The quantitative variables were expressed as medians for nonparametric data, or as means for parametric data, and coefficient of variation (CV). The qualitative variables were expressed as absolute numbers and percentages. In the second step, the patients were divided into two groups, one group of those who developed AF and the other group of those who did not developed AF, and the following variables were compared between the new groups: age, in-hospital death, post-CABG hospital length of stay (days), number of grafts, and use of CPB. Their statistical analysis was performed with the MedCalc software. The qualitative variables were assessed by using two-tailed Fisher exact test. The quantitative variables had their normality tested by use of Shapiro-Wilk test; because the data had nonparametric distribution, they were assessed by use of two-tailed Mann-Whitney test. To assess the effect size, absolute risk reduction (ARR) and relative risk reduction (RRR) were used, and, for qualitative variables, the number needed to treat (NNT). The statistical significance level adopted was p &lt; 0.05.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>The sample comprised 140 patients randomized into two groups, with 70 patients each: G15, CVP maintained &#8804; 15 cmH<sub>2</sub>O; and G20, CVP maintained &#8804; 20 cmH<sub>2</sub>O. The comparative analysis of patients' age and sex is shown in <xref ref-type="table" rid="t1">Table 1</xref>. The mean ages of the groups were 60 years (CV = 0.17) in G15, and 63 years (CV = 0.15) in G20 (p = 0.6). The male sex predominated in both groups (G15=67.10%; and G20 = 81.43%; p = 0.07).</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Patients' age and sex according to group (G15: CVP control &#8804; 15 cmH<sub>2</sub>O; and G20: CVP control &#8804; 20 cmH<sub>2</sub>O)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Variables</th>
              <th align="center">G15 (n = 70)</th>
              <th align="center">G20 (n = 70)</th>
              <th align="center">p</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Age, mean (CV)</td>
              <td align="center">60 (0.17)</td>
              <td align="center">63 (0.15)</td>
              <td align="center">0.6 <sup><xref ref-type="table-fn" rid="TFN2">&#8224;</xref></sup></td>
            </tr>
            <tr>
              <td align="left">Male sex, n (%)</td>
              <td align="center">47 (67.1)</td>
              <td align="center">57 (81.43)</td>
              <td align="center">0.07<xref ref-type="table-fn" rid="TFN1">*</xref>
							</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <label>(*)</label>
            <p>Fisher exact test (two-tailed);</p>
          </fn>
          <fn id="TFN2">
            <label>(&#8224;)</label>
            <p>Mann-Whitney test (two-tailed); CVP: central venous pressure; CV: coefficient of variation.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>The analysis of comorbidities evidenced no statistical difference between the groups (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
      <table-wrap id="t2">
        <label>Table 2</label>
        <caption>
          <title>Assessed comorbidities according to group (G15: CVP control &#8804; 15 cmH<sub>2</sub>O; and G20: CVP control &#8804; 20 cmH<sub>2</sub>O)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Variables</th>
              <th align="center">G15 (n = 70)</th>
              <th align="center">G20 (n = 70)</th>
              <th align="center">p</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Diabetes mellitus, n (%)</td>
              <td align="center">18 (25.71)</td>
              <td align="center">25 (35.71)</td>
              <td align="center">0.07<xref ref-type="table-fn" rid="TFN3">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">COPD, n (%)</td>
              <td align="center">10 (14.28)</td>
              <td align="center">11 (15.71)</td>
              <td align="center">1.00<xref ref-type="table-fn" rid="TFN3">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">Peripheral arterial disease, n (%)</td>
              <td align="center">7 (10.00)</td>
              <td align="center">12 (17.14)</td>
              <td align="center">0.27<xref ref-type="table-fn" rid="TFN3">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">Previous recent AMI, n (%)</td>
              <td align="center">28 (40)</td>
              <td align="center">23 (32.85)</td>
              <td align="center">0.48<xref ref-type="table-fn" rid="TFN3">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">LVD (EF &lt; 50%), n (%)</td>
              <td align="center">8 (11.42)</td>
              <td align="center">16 (22.85)</td>
              <td align="center">0.11<xref ref-type="table-fn" rid="TFN3">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">Renal function (GFR), mL/min (CV)</td>
              <td align="center">85.78 (0.37)</td>
              <td align="center">88.32 (0.49)</td>
              <td align="center">0.48 <sup><xref ref-type="table-fn" rid="TFN4">&#8224;</xref></sup></td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN3">
            <label>(*)</label>
            <p>Fisher exact test (two-tailed);</p>
          </fn>
          <fn id="TFN4">
            <label>(&#8224;)</label>
            <p>Mann-Whitney test (two-tailed); CVP: central venous pressure; COPD: chronic obstructive pulmonary disease; AMI: acute myocardial infarction; LVD: left ventricular dysfunction; EF: ejection fraction; CV: coefficient of variation; GFR: glomerular filtration rate.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>In the 48-72 post-CABG hours, the incidence of AF differed statistically between the groups (<xref ref-type="table" rid="t3">Table 3</xref>). In G15, 8.56% of the patients developed AF, in contrast to 22.86% of those in G20 (p = 0.03). The ARR was 14.28% [95% confidence interval (95% CI): 2.14-26.28], and RRR were used of 62.50% (95% CI: 9.79-84.41) and NNT of 7. The sample power was 64.40%.</p>
      <table-wrap id="t3">
        <label>Table 3</label>
        <caption>
          <title>Comparison of atrial fibrillation within 72 postoperative hours, in-hospital death, hospital length of stay after coronary artery bypass grafting, number of grafts and use of cardiopulmonary bypass between patients with CVP control &#8804; 15 cmH<sub>2</sub>O (G15) and CVP control &#8804; 20 cmH<sub>2</sub>O (G20)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Variables</th>
              <th align="center">G15 (n = 70)</th>
              <th align="center">G20 (n = 70)</th>
              <th align="center">p</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Atrial fibrillation, n (%)</td>
              <td align="center">6 (8.57)</td>
              <td align="center">16 (22.86)</td>
              <td align="center">0.03<xref ref-type="table-fn" rid="TFN5">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">In-hospital death, n (%)</td>
              <td align="center">4 (5.71)</td>
              <td align="center">8 (11.42)</td>
              <td align="center">0.07<xref ref-type="table-fn" rid="TFN5">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">Hospital length of stay, mean, days (CV)</td>
              <td align="center">7.14 (0.70)</td>
              <td align="center">8.21 (0.68)</td>
              <td align="center">0.36<sup><xref ref-type="table-fn" rid="TFN6">&#8224;</xref></sup></td>
            </tr>
            <tr>
              <td align="left">Grafts, median</td>
              <td align="center">3</td>
              <td align="center">2</td>
              <td align="center">0.22 <sup><xref ref-type="table-fn" rid="TFN6">&#8224;</xref></sup></td>
            </tr>
            <tr>
              <td align="left">Cardiopulmonary bypass, n (%)</td>
              <td align="center">47 (67.10)</td>
              <td align="center">39 (55.70)</td>
              <td align="center">0.22<xref ref-type="table-fn" rid="TFN5">*</xref>
							</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN5">
            <label>(*)</label>
            <p>Fisher exact test (two-tailed);</p>
          </fn>
          <fn id="TFN6">
            <label>(&#8224;)</label>
            <p>Mann-Whitney test (two-tailed); CVP: central venous pressure; CV: coefficient of variation.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>In G15, there were 4 in-hospital deaths, 2 due to pulmonary sepsis and 2 due to stroke. In G20, there were 8 in-hospital deaths, 5 due to stroke, 2 due to pulmonary sepsis and 1 due to urinary sepsis. Mortality showed no statistical difference (p = 0.07). In addition, there was no difference regarding the post-CABG hospital length of stay (days), number of grafts, and use of CPB.</p>
      <p>In the group of patients who developed AF, the following variables were analyzed: mortality, hospital length of stay, number of grafts, and use of CPB (<xref ref-type="table" rid="t4">Table 4</xref>). Age differed statistically between the groups (p = 0.04), with mean of 65.68 years among patients who developed AF, and of 60.73 among those who did not develop AF. The hospital length of stay was significant (p = 0.0012) among patients who developed AF, with mean of 10.22 days (CV = 0.70). The other variables were statistically similar.</p>
      <table-wrap id="t4">
        <label>Table 4</label>
        <caption>
          <title>Comparison of age, mortality, hospital length of stay, number of grafts and use of cardiopulmonary bypass between patients who developed atrial fibrillation (AF) and those who did not</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Variables</th>
              <th align="center">With AF (n = 22; 15.17%)</th>
              <th align="center">Without AF (n = 118; 84.29%)</th>
              <th align="center">p</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Age, mean (CV)</td>
              <td align="center">65.68 (0.15)</td>
              <td align="center">60.73 (0.16)</td>
              <td align="center">0.04</td>
            </tr>
            <tr>
              <td align="left">In-hospital death, n (%)</td>
              <td align="center">2 (5.71%)</td>
              <td align="center">10 (11.42%)</td>
              <td align="center">1.00<xref ref-type="table-fn" rid="TFN7">*</xref>
							</td>
            </tr>
            <tr>
              <td align="left">Hospital length of stay, mean, days (CV)</td>
              <td align="center">10.22 (0.70)</td>
              <td align="center">7.20 (0.67)</td>
              <td align="center">0.001<sup><xref ref-type="table-fn" rid="TFN8">&#8224;</xref></sup></td>
            </tr>
            <tr>
              <td align="left">Grafts, median</td>
              <td align="center">2</td>
              <td align="center">2</td>
              <td align="center">0.69<sup><xref ref-type="table-fn" rid="TFN8">&#8224;</xref></sup></td>
            </tr>
            <tr>
              <td align="left">Cardiopulmonary bypass, n (%)</td>
              <td align="center">12 (54.55)</td>
              <td align="center">74 (62.71)</td>
              <td align="center">0.48<xref ref-type="table-fn" rid="TFN7">*</xref>
							</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN7">
            <label>(*)</label>
            <p>Fisher exact test (two-tailed);</p>
          </fn>
          <fn id="TFN8">
            <label>(&#8224;)</label>
            <p>Mann-Whitney test (two-tailed); CV: coefficient of variation.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>This study compared the AF incidence in the first 72 post-CABG hours using two CVP control strategies, based on intention to treat, that is, the use of a diuretic was aimed at maintaining CVP below the cutoff points. Patients maintained with CVP &#8804; 15 cmH<sub>2</sub>O in that period had lower AF incidence as compared to patients whose CVP was maintained &#8804; 20 cmH<sub>2</sub>O (8.56% vs. 22.86%; p = 0.03). Measures of effect size were relevant: ARR of group G15 was 12.12%, equivalent to a NNT of 7, that is, 1 in every 7 patients benefited from CVP control &#8804; 15 cmH<sub>2</sub>O after CABG, suggesting that maintaining CVP under control can be effective in reducing AF incidence. The AF incidences in each group and in the whole sample (15.71%) are similar to those reported in the literature (5-40%).<xref ref-type="bibr" rid="B4">4</xref> The CVP was measured with a monitor in mm Hg and in water column; we chose to use the water column measure because some patients had only 24 hours of mmHg monitoring. For patients stable after 24 hours, it is routine procedure to end invasive blood pressure monitoring, CVP being controlled only by use of water column.</p>
      <p>Atrial fibrillation in the PO period increases the risk for ischemic stroke, ventricular tachycardia, ventricular fibrillation, hypotension and heart failure.<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> Post-CABG AF is associated with increased hospital length of stay after surgery and in-hospital mortality.<xref ref-type="bibr" rid="B6">6</xref> Sobral et al.<xref ref-type="bibr" rid="B9">9</xref> have reported a longer hospital length of stay of patients with AF (mean of 16.4 days; p = 0.004); however, they have not established whether AF was the cause of prolonged hospitalization or an indicator of the severity of more critically-ill patients. In addition, they have reported a peak incidence of 2.6 days (median, 2 days). Da Silva et al.<xref ref-type="bibr" rid="B10">10</xref> have shown a mean hospital length of stay of patients who developed AF after cardiac surgery of 16.9 days (p = 0.001). In their sample, the hospital length of stay was significantly longer among patients with AF (p = 0.0012). They have not assessed the peak incidence in relation to that time, but the period studied (72 hours) is in accordance with the predicted time in the literature for higher AF incidence.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> The mortality rate reported by Sobral et al.<xref ref-type="bibr" rid="B9">9</xref> 1 year after surgery was 4.7% (n = 109; p = 0.001) for patients who developed AF, with a 30-day rehospitalization rate of 7.6% (n = 168; p = 0.004) and an 1-year rehospitalization rate of 18.7% (n = 417; p = 0.004). In our sample, in-hospital mortality and hospital length of stay were assessed, and were slightly higher in G20, but with no statistical difference.</p>
      <p>Knowing the risk factors for post-CABG AF is highly important. It enables the use of prophylactic measures, aimed at reducing the incidence of AF, as well as of its complications.<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
			</p>
      <p>Some risk factors for AF have been demonstrated. Age over 65 years<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> has been reported as one of the most important risk factors.<xref ref-type="bibr" rid="B7">7</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> Age is associated with myocardial structural changes due to degenerative processes (fibrosis and dilatation), which lead to lack of an effective refractory period, dispersion of atrial refractoriness and abnormal conduction and automaticity.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> In addition, advanced age is related to increased in-hospital mortality.<xref ref-type="bibr" rid="B9">9</xref> In our study, mean age was 60 years in G15, and 63 years in G20, with no statistical difference (p = 0.07). Age showed significance when analyzing patients who developed AF as compared to those who did not (p = 0.04). The mean age of those who developed AF was 66 years, similarly to that reported in the literature.<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>
			</p>
      <p>Diabetes mellitus leads to metabolic changes, such as increased oxidative stress, elevated levels of free fatty acids, and chronic tissue inflammation. Such alterations result in changes in atrial structure and electrical conduction, contributing to AF development in the PO period.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> In our sample, the prevalence of diabetes mellitus was similar in both groups (p = 0.07).</p>
      <p>Peripheral arterial occlusive disease associates with the severity of the patients' clinical profile and comorbidities that predispose to the appearance of AF after cardiac surgery.<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> El-Chami et al.<xref ref-type="bibr" rid="B14">14</xref> have identified peripheral arterial disease as a risk factor for AF, and considered it an independent predictor of mortality. In our study, the peripheral arterial occlusive disease prevalence did not statistically differ between the groups.</p>
      <p>Other conditions associated with the development of post-CABG AF are COPD,<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref> chronic renal failure,<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> previous AMI,<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> and left ventricular dysfunction.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> The prevalence of those risk factors was similar in both groups.</p>
      <p>The number of grafts performed during CABG and the use of CPB have been identified as risk factors,<xref ref-type="bibr" rid="B7">7</xref> but with some disagreement between different authors.<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref> The CPB is an invasive technique related to atrial ischemia and inflammatory response in the PO period of cardiac surgeries.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B20">20</xref> The groups studied showed no statistical difference regarding those parameters.</p>
      <p>Some strategies for post-CABG AF prevention have been developed, especially those related to pharmacological prophylaxis. Beta-blockers are the drugs of choice, because they significantly reduce the AF incidence, being related to lower PO morbidity and mortality.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref> They belong to the most studied and used drug class, especially because of the control they have on the increased sympathetic tone in patients submitted to cardiac surgery.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Beta-blockers are indicated for all patients undergoing CABG, except in the presence of contraindications.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref> Prophylaxis with amiodarone and intravenous magnesium is recommended when beta-blockers are contraindicated.<xref ref-type="bibr" rid="B22">22</xref> In older studies, the use of statins in the preoperative and PO periods was considered relevant to post-CABG AF prevention. Those drugs act by reducing the inflammation of patients with coronary arterial disease. A meta-analysis by Zheng et al.<xref ref-type="bibr" rid="B23">23</xref> has shown that statin therapy significantly reduced the AF incidence and hospital length of stay. Bockeria et al.<xref ref-type="bibr" rid="B24">24</xref> have shown that patients receiving statin before CABG had higher benefits in preventing early AF than those who did not. However, the literature is still controversial. In a recent meta-analysis,<xref ref-type="bibr" rid="B25">25</xref> the authors have concluded that PO statin therapy does not prevent AF in patients undergoing elective cardiac surgery. At our service, the use of beta-blockers and statins is maintained in the preoperative period and reintroduced with diet usually on the first PO day. If the patient is on dobutamine or noradrenaline, the beta-blocker is introduced after suspension of the vasoactive drug.</p>
      <p>CVP is an important predictor of early mortality, independently of cardiac output and other variable clinical conditions, mainly in the first 6 PO hours, because of hemodynamic instability.<xref ref-type="bibr" rid="B26">26</xref> Strict CVP control is aimed at measuring the pressure to which the atria are submitted, taking the intravascular volume into consideration. The result of the intravascular volume overload is hypertension, atrial dilatation and contraction reduction, because of stretching of cardiac muscle fibers. However, that can be reversed with diuretics.<xref ref-type="bibr" rid="B26">26</xref><sup>-</sup><xref ref-type="bibr" rid="B28">28</xref> Kalus et al.<xref ref-type="bibr" rid="B29">29</xref> have shown that hemodynamic control based on the administration of large amounts of fluids accounted for the increase in atrial pressure, and could trigger AF in the PO period of cardiothoracic surgery. They have observed that cardiothoracic surgery patients who developed AF had received approximately 1 liter of fluids more than those who did not develop that arrhythmia, and that difference was more significant on the second PO day (p = 0.04). The limiting factor of that study was the lack of documentation of the increase in atrial pressure and volume after surgery.</p>
      <p>Intravascular volume overload causes abnormal dispersion of atrial refractory period, because of the increase in atrial volume and pressure. Thus, the atrium becomes vulnerable to the development of AF.<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B30">30</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref> Hwang et al.<xref ref-type="bibr" rid="B31">31</xref> have suggested that intravascular volume is an important parameter, as are arterial gas analysis, hemoglobin and serum potassium, which should be assessed when there is post-CABG AF, because they can clarify the reversible causes of that arrhythmia. In addition, Silva et al.<xref ref-type="bibr" rid="B10">10</xref> have shown that excessive fluid balance in the first 24 PO hours is a risk factor for post-CABG AF. Those authors have reported pulmonary congestion as a trigger for that arrhythmia. Koletsis et al.<xref ref-type="bibr" rid="B15">15</xref> have reported an association between positive fluid balance, reflecting an excessive intravascular volume, and occurrence of post-CABG AF. In addition, the positive fluid balance has been accounted for the increase in left atrial pressure and pulmonary congestion, leading to hypoxia.</p>
      <p>The increased left atrial volume identified in the preoperative period predisposes to the development of AF after cardiac surgery. Wang et al.<xref ref-type="bibr" rid="B32">32</xref> have shown that the left atrial expansion index was associated with in-hospital mortality and post-CABG AF, being an independent risk factor. Osranek et al.<xref ref-type="bibr" rid="B16">16</xref> have reported that an increase over 32 mL/m<sup>2</sup> in left ventricular volume increases by 5 times the risk for AF, as a factor independent of age and other surgical parameters. Patel et al.<xref ref-type="bibr" rid="B33">33</xref> have found that for every 5-mm increase in the left atrium, on the echocardiogram, the risk for AF increases by 39%. Sanfilippo et al.<xref ref-type="bibr" rid="B30">30</xref> have concluded that maintaining sinus rhythm prevents the progression of left atrial hypertrophy and its adverse effects. Maceira et al.<xref ref-type="bibr" rid="B34">34</xref> have studied the right atrial dimensions by use of magnetic resonance imaging. The best independent indicators of increased atrial volume were area greater than 16 cm<sup>2</sup>/m<sup>2</sup> and longitudinal diameter greater than 3.5 cm/m<sup>2</sup>. The present study did not assess left atrial volume in the preoperative period, because not all patients underwent echocardiography before surgery.</p>
      <p>In our study, CVP maintained &#8804; 15 cmH<sub>2</sub>O proved to be important to prevent post-CABG AF, as compared to CVP &#8804; 20 cmH<sub>2</sub>O. The statistical power of the sample was satisfactory (66.70%); however, further studies, with larger samples, are required to validate that approach as a prophylactic measure against AF in the PO period of cardiac surgery. Our data suggest that stricter CVP control is advantageous to prevent excessive volume overloads. Neither mortality after discharge, nor the appearance of AF after that have been assessed. Another study<xref ref-type="bibr" rid="B35">35</xref> has shown that strict CVP control can prevent post-CABG AF as compared to no CVP control. Our study strategy proved beneficial (NNT = 7) in this relatively small sample (140 patients) in a single-center study.</p>
      <p>Multicenter studies with a larger sample that can assess not only AF incidence, but also mortality and the increase in costs with longer hospital length of stay, are required to better assess this type of treatment. It is worth noting that the use of diuretics caused no harm to the patients, there was increase in neither renal failure nor hemodynamic instability, in addition to being a very low cost strategy. Thus, CVP control can serve as a complementary method in post-CABG AF prophylaxis.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>The CVP control maintained &#8804; 15 cmH<sub>2</sub>O, in the first 48-72 PO hours, can reduce the incidence of post-CABG AF. One in every seven patients benefits from that strategy.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This study is not associated with any thesis or dissertation work.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
          <subj-group>
            <subject>Cirurgia Card&#237;aca - Adultos</subject>
          </subj-group>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Compara&#231;&#227;o de Duas Estrat&#233;gias de Controle de Press&#227;o Venosa Central na Preven&#231;&#227;o de Fibrila&#231;&#227;o Atrial em P&#243;s-Operat&#243;rio de Revasculariza&#231;&#227;o do Mioc&#225;rdio</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Mario Augusto Cray da</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lirani</surname>
            <given-names>Wesley</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wippich</surname>
            <given-names>Ana Caroline</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Luana</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tolentino</surname>
            <given-names>Eduardo de Souza</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Zampar</surname>
            <given-names>Beatriz</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Schafranski</surname>
            <given-names>Marcelo Derbli</given-names>
          </name>
          <xref ref-type="aff" rid="aff2"/>
        </contrib>
        <aff id="aff2">
          <institution content-type="original">Universidade Estadual de Ponta Grossa, Ponta Grossa, PR - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Mario Augusto Cray da Costa</bold>, Rua Coronel Bittencourt, 567. CEP 84010-290, Centro, Ponta Grossa, PR - Brasil. E-mail: <email>drmarioaugusto@uol.com.br</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Costa MAC, Lirani W, Wippich AC, Schafranski MD; Obten&#231;&#227;o de dados, An&#225;lise estat&#237;stica, An&#225;lise e interpreta&#231;&#227;o dos dados, Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Costa MAC, Lirani W, Wippich AC, Lopes L, Tolentino ES, Zampar B, Schafranski MD; Obten&#231;&#227;o de financiamento: Costa MAC, Lirani W, Schafranski MD.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A fibrila&#231;&#227;o atrial (FA) ocorre em 10-40% dos pacientes submetidos a cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica (RM), e eleva a mortalidade cardiovascular. Como o aumento dos &#225;trios est&#225; associado ao aumento da incid&#234;ncia de FA, espera-se que pacientes com press&#227;o venosa central (PVC) mais alta tenham maior distens&#227;o atrial, o que eleva a incid&#234;ncia dessa arritmia.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Comparar a incid&#234;ncia de FA em p&#243;s-operat&#243;rio de RM, seguindo duas estrat&#233;gias de controle de PVC.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Estudo cl&#237;nico randomizado controlado intervencionista. A amostra foi composta por 140 pacientes submetidos a RM entre 2011 e 2015. Os pacientes foram randomizados em dois grupos, G15 e G20, mantidos com PVC m&#225;xima de 15 cmH<sub>2</sub>O e 20 cmH<sub>2</sub>O, respectivamente.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Foram inclu&#237;dos 70 pacientes em cada grupo. A incid&#234;ncia da arritmia em G15 foi de 8,57% e, no G20, de 22,86%, com redu&#231;&#227;o de risco absoluto de 14,28% e n&#250;mero necess&#225;rio para tratar (NNT) de 7 (p = 0,03). Mortalidade (G15 = 5,71%; G20 = 11,42%; p = 0,07), tempo de internamento (G15 = 7,14 dias; G20 = 8,21 dias; p = 0,36), n&#250;mero de enxertos (medianas: G15 = 3, G2 = 2; p = 0,22) e uso de circula&#231;&#227;o extracorp&#243;rea (G15 = 67,10%; G20 = 55,70%; p = 0,22) mostraram-se estatisticamente semelhantes. A idade (p = 0,04) e o tempo de internamento (p = 0,001) foram significativamente maiores nos pacientes que desenvolveram FA nos dois grupos.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Manter a PVC com valores mais baixos nas primeiras 72h ap&#243;s a cirurgia de RM reduz o risco relativo de FA e pode ser uma ferramenta &#250;til na preven&#231;&#227;o da FA ap&#243;s RM. </p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Press&#227;o Venosa Central</kwd>
        <kwd>Fibrila&#231;&#227;o Atrial/preven&#231;&#227;o</kwd>
        <kwd>Revasculariza&#231;&#227;o do Mioc&#225;rdio</kwd>
        <kwd>Cuidados P&#243;s Operat&#243;rios</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A fibrila&#231;&#227;o atrial (FA) &#233; uma arritmia que ocorre devido &#224; aus&#234;ncia de despolariza&#231;&#227;o ordenada, causando perda da capacidade de contra&#231;&#227;o dos &#225;trios. Est&#225; relacionada ao risco aumentado de acidente vascular cerebral (AVC) e de mortalidade.<xref ref-type="bibr" rid="B1">1</xref><sup>-</sup><xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>A FA no p&#243;s-operat&#243;rio de revasculariza&#231;&#227;o do mioc&#225;rdio (FAPORM) ocorre em 5-40% dos pacientes, em geral entre o segundo e o quarto dia de p&#243;s-operat&#243;rio (PO), com pico de incid&#234;ncia no segundo dia.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> A fisiopatologia &#233; multifatorial e inclui estresse oxidativo, resposta inflamat&#243;ria sist&#234;mica, produ&#231;&#227;o excessiva de catecolaminas, mudan&#231;as no t&#244;nus auton&#244;mico e na express&#227;o de conexinas. Esses fatores promovem a dispers&#227;o refrat&#225;ria atrial, alteram sua condu&#231;&#227;o el&#233;trica e predisp&#245;em &#224; arritmia.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>Alguns fatores de risco est&#227;o relacionados &#224; maior incid&#234;ncia de FAPORM: idade avan&#231;ada, doen&#231;a vascular perif&#233;rica, doen&#231;a pulmonar cr&#244;nica, diabetes mellitus, hipertens&#227;o arterial sist&#234;mica, cardiopatia valvar, aumento de &#225;trio esquerdo, disfun&#231;&#227;o ventricular esquerda, hist&#243;rico de FA ou infarto agudo do mioc&#225;rdio (IAM) pr&#233;vios, suspens&#227;o de f&#225;rmacos beta-bloqueadores na fase pr&#233;-operat&#243;ria, utiliza&#231;&#227;o de circula&#231;&#227;o extracorp&#243;rea (CEC) e aumento do t&#244;nus simp&#225;tico no PO.<xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref>
				</p>
        <p>A FAPORM piora o estado hemodin&#226;mico do paciente, devido ao aumento do risco de insufici&#234;ncia card&#237;aca congestiva e eventos emb&#243;licos em longo prazo. O AVC &#233; uma das principais complica&#231;&#245;es, observado em 2% dos pacientes operados. Al&#233;m disso, foi associado com maior mortalidade intra-hospitalar e pior sobrevida em longo prazo.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> Essas complica&#231;&#245;es justificam a necessidade de introduzir medidas profil&#225;ticas para FAPORM.</p>
        <p>O racional desta pesquisa baseia-se na seguinte hip&#243;tese: como o aumento do volume dos &#225;trios associa-se ao aumento da incid&#234;ncia de FA,<xref ref-type="bibr" rid="B8">8</xref> espera-se que pacientes com press&#227;o venosa central (PVC) mais alta tenham maior distens&#227;o atrial e, consequentemente, maior incid&#234;ncia de FA, al&#233;m de maior predisposi&#231;&#227;o &#224; congest&#227;o pulmonar, hipoxemia e edema da parede atrial, fatores que contribuem para aumento da arritmia. Assim, o controle da PVC poderia ser uma ferramenta &#250;til na preven&#231;&#227;o de FAPORM. Com o objetivo de testar essa hip&#243;tese, foi avaliada a incid&#234;ncia de FAPORM em pacientes submetidos &#224; RM, sob duas estrat&#233;gias de controle de PVC.</p>
      </sec>
      <sec>
        <title>Objetivo</title>
        <p>O objetivo deste trabalho &#233; analisar se h&#225; diferen&#231;a entre duas estrat&#233;gias de controle de PVC (baseado na inten&#231;&#227;o de tratar) na incid&#234;ncia de FA em 48 a 72h de PO de RM, comparando dois grupos: G15 (PVC &#8804; 15 cmH<sub>2</sub>O) e G20 (PVC &#8804; 20 cmH<sub>2</sub>O), sendo FA o desfecho prim&#225;rio. O desfecho secund&#225;rio foi comparar, entre os grupos, o tempo de internamento no PO e a mortalidade.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Tipo de estudo</title>
          <p>Trata-se de um estudo cl&#237;nico, randomizado, controlado, intervencionista e prospectivo, realizado na Unidade de Terapia Intensiva (UTI) da Santa Casa de Miseric&#243;rdia de Ponta Grossa em parceria com a Universidade Estadual de Ponta Grossa (UEPG). A an&#225;lise foi realizada com informa&#231;&#245;es coletadas pelos pesquisadores prospectivamente. Este projeto foi aprovado pelo Comit&#234; de &#201;tica e Pesquisa UEPG, segue os padr&#245;es da Declara&#231;&#227;o de Helsinki de 1975 e todos os pacientes inclu&#237;dos assinaram o Termo de Consentimento Livre e Esclarecido antes do procedimento cir&#250;rgico.</p>
        </sec>
        <sec>
          <title>Crit&#233;rios de inclus&#227;o e exclus&#227;o</title>
          <p>A amostra foi composta por pacientes submetidos &#224; RM pelo servi&#231;o de Cirurgia Card&#237;aca da Santa Casa de Miseric&#243;rdia de Ponta Grossa no per&#237;odo de janeiro de 2011 a dezembro de 2015.</p>
          <p>Foram exclu&#237;dos pacientes com as seguintes caracter&#237;sticas: submetidos &#224; RM associada a outro procedimento; hist&#243;ria de FA no pr&#233;-operat&#243;rio; contraindica&#231;&#227;o em manter PVC abaixo dos valores preconizados (como hipertens&#227;o pulmonar grave); insufici&#234;ncia renal cr&#244;nica grave, determinada por ritmo de filtra&#231;&#227;o glomerular &lt; 30 ml/min; disfun&#231;&#227;o ventricular esquerda grave; em uso de f&#225;rmacos vasoativos em doses altas, como dopamina ou dobutamina &gt; 7mcg/kg/min ou noradrenalina &gt; 0,7mcg/kg/min; sem uso de betabloqueador ou estatina no pr&#233;-operat&#243;rio ou sem reintrodu&#231;&#227;o da dieta e ap&#243;s suspens&#227;o de f&#225;rmaco vasoativo no PO; necessidade maior do que 20 ampolas de furosemida em 24 horas para manter os n&#237;veis de PVC.</p>
        </sec>
        <sec>
          <title>Desfechos</title>
          <p><bold>Desfecho prim&#225;rio:</bold> aparecimento de FA em 48 a 72 horas de PO, vista ao cardiosc&#243;pio de monitoriza&#231;&#227;o cont&#237;nua e documentada com ECG de 12 deriva&#231;&#245;es.<xref ref-type="bibr" rid="B9">9</xref>
					</p>
          <p><bold>Desfechos secund&#225;rios:</bold> mortalidade hospitalar e tempo de internamento no PO.</p>
        </sec>
        <sec>
          <title>Padroniza&#231;&#227;o dos grupos e coleta de dados</title>
          <p>Os pacientes foram randomizados em dois grupos, por meio de sorteio: G15, com meta de PVC igual ou inferior a 15 cmH<sub>2</sub>O; e G20, com PVC igual ou inferior a 20 cmH<sub>2</sub>O. A estrat&#233;gia de controle de PVC consistiu em medir a press&#227;o de 2/2h durante 72 horas de PO, ou at&#233; a alta da UTI. O tempo m&#237;nimo de perman&#234;ncia na UTI foi de 48 horas. Toda vez que a PVC atingiu seu ponto de corte, foi administrada uma ampola endovenosa de furosemida, a partir da sexta hora, visto que nas primeiras 6 horas do PO h&#225; maior instabilidade hemodin&#226;mica. Drogas vasoativas ou anti-hipertensivas foram utilizadas para manter press&#227;o arterial m&#233;dia (PAM) de 60-100 mmHg. Comparou-se a incid&#234;ncia de FA entre os dois grupos, detectada por monitoriza&#231;&#227;o eletrocardiogr&#225;fica cont&#237;nua (cardiosc&#243;pio) e confirmada por eletrocardiograma de 12 deriva&#231;&#245;es.</p>
          <p>Os seguintes dados foram coletados diariamente pelos pesquisadores: medidas de PVC, necessidade de furosemida, ocorr&#234;ncia de FA no per&#237;odo m&#237;nimo (48h) e m&#225;ximo (72h) de PO, tempo de internamento e &#243;bito hospitalar.<xref ref-type="bibr" rid="B9">9</xref> Os dados de cirurgia e comorbidades foram coletados da ficha padr&#227;o de pr&#233;-operat&#243;rio e PO dos pacientes como: idade, sexo, FA pr&#233;via, diabetes mellitus, doen&#231;a pulmonar obstrutiva cr&#244;nica (DPOC), doen&#231;a renal cr&#244;nica, doen&#231;a vascular perif&#233;rica, fun&#231;&#227;o do ventr&#237;culo esquerda, IAM recente, uso de CEC e n&#250;mero de pontes.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>Foi realizada em duas etapas. Na primeira, foram comparadas, entre os grupos G15 e G20, as vari&#225;veis: idade, sexo, diabetes mellitus, DPOC, arteriopatia perif&#233;rica, IAM recente nos &#250;ltimos tr&#234;s meses antes da cirurgia, presen&#231;a de disfun&#231;&#227;o ventricular esquerda moderada (fra&#231;&#227;o de eje&#231;&#227;o menor que 50% e maior que 35%), ritmo de filtra&#231;&#227;o glomerular, incid&#234;ncia de FA, &#243;bito hospitalar, dias de internamento no PO, n&#250;mero de enxertos e uso de CEC. As vari&#225;veis quantitativas foram apresentadas em mediana para os dados n&#227;o param&#233;tricos, ou m&#233;dia para os dados param&#233;tricos e coeficiente de varia&#231;&#227;o (CV). As vari&#225;veis qualitativas foram apresentadas em n&#250;meros absolutos e porcentagens. Na segunda etapa, os pacientes foram reagrupados em dois grupos sendo um dos que desenvolveram FA e o outro daqueles que n&#227;o desenvolveram FA, comparando-se entre esses grupos as vari&#225;veis: idade, &#243;bito hospitalar, dias de internamento no PO, n&#250;mero de enxertos, uso de CEC. A an&#225;lise estat&#237;stica dos mesmos foi realizada com aux&#237;lio do software MedCalc. Vari&#225;veis qualitativas foram avaliadas pelo teste exato de Fisher (bicaudado). Vari&#225;veis quantitativas tiveram a normalidade testada pelo teste de Shapiro-Wilk e, como os dados apresentaram distribui&#231;&#227;o n&#227;o param&#233;trica, foram avaliadas pelo teste de Mann-Whitney (bicaudado). Para avaliar o tamanho de efeito, utilizou-se a redu&#231;&#227;o do risco absoluto (RRA) e redu&#231;&#227;o de risco relativo (RRR), para vari&#225;veis qualitativas, n&#250;mero necess&#225;rio para tratar (NNT). Foi considerado estatisticamente significante p &lt; 0,05.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>A amostra foi composta por 140 pacientes randomizados em dois grupos, com 70 pacientes cada: G15, no qual foram mantidos com PVC igual ou inferior a 15 cmH<sub>2</sub>O; e G20, com PVC igual ou inferior a 20 cmH<sub>2</sub>O. A an&#225;lise comparativa entre idade e sexo dos pacientes encontra-se na <xref ref-type="table" rid="t5">Tabela 1</xref>. A idade m&#233;dia dos grupos foi de 60 anos (CV = 0,17) em G15 e 63 anos (CV = 0,15) em G20 (p = 0,6). O sexo masculino predominou em ambos os grupos (G15 = 67,10%; e G20 = 81,43%; p = 0,07).</p>
        <table-wrap id="t5">
          <label>Tabela 1</label>
          <caption>
            <title>Idade e sexo dos pacientes nos dois grupos estudados (G15: PVC mantida &#8804; 15 cmH<sub>2</sub>O; e G20: CVP mantida &#8804; 20 cmH<sub>2</sub>O)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Vari&#225;vel</th>
                <th align="center">G15 (n = 70)</th>
                <th align="center">G20 (n = 70)</th>
                <th align="center">p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Idade, m&#233;dia (CV)</td>
                <td align="center">60 (0,17)</td>
                <td align="center">63 (0,15)</td>
                <td align="center">0,6 <sup><xref ref-type="table-fn" rid="TFN10">&#8224;</xref></sup></td>
              </tr>
              <tr>
                <td align="left">Sexo masculino, n (%)</td>
                <td align="center">47 (67,1)</td>
                <td align="center">57 (81,43)</td>
                <td align="center">0,07<xref ref-type="table-fn" rid="TFN9">*</xref>
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN9">
              <label>(*)</label>
              <p>Teste exato de Fisher (bicaudado);</p>
            </fn>
            <fn id="TFN10">
              <label>(&#8224;)</label>
              <p>Teste de Mann-Whitney (bicaudado); PVC: press&#227;o venosa central; CV: coeficiente de varia&#231;&#227;o.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A an&#225;lise das comorbidades (<xref ref-type="table" rid="t6">Tabela 2</xref>) n&#227;o evidenciou diferen&#231;as estat&#237;sticas entre os grupos.</p>
        <table-wrap id="t6">
          <label>Tabela 2</label>
          <caption>
            <title>Comorbidades avaliadas nos dois grupos estudados (G15: PVC mantida &#8804; 15 cmH<sub>2</sub>O; e G20: CVP mantida &#8804; 20 cmH<sub>2</sub>O)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Vari&#225;vel</th>
                <th align="center">G15 (n = 70)</th>
                <th align="center">G20 (n = 70)</th>
                <th align="center">p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Diabetes mellitus, n (%)</td>
                <td align="center">18 (25,71)</td>
                <td align="center">25 (35,71)</td>
                <td align="center">0,07<xref ref-type="table-fn" rid="TFN11">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">DPOC, n (%)</td>
                <td align="center">10 (14,28)</td>
                <td align="center">11 (15,71)</td>
                <td align="center">1,00<xref ref-type="table-fn" rid="TFN11">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">Arteriopatia perif&#233;rica, n (%)</td>
                <td align="center">7 (10,00)</td>
                <td align="center">12 (17,14)</td>
                <td align="center">0,27<xref ref-type="table-fn" rid="TFN11">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">IAM recente pr&#233;vio, n (%)</td>
                <td align="center">28 (40)</td>
                <td align="center">23 (32,85)</td>
                <td align="center">0,48<xref ref-type="table-fn" rid="TFN11">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">DVE (FE &lt; 50%), n (%)</td>
                <td align="center">8 (11,42)</td>
                <td align="center">16 (22,85)</td>
                <td align="center">0,11<xref ref-type="table-fn" rid="TFN11">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">Fun&#231;&#227;o renal (RFG), ml/min (CV)</td>
                <td align="center">85,78 (0,37)</td>
                <td align="center">88,32 (0,49)</td>
                <td align="center">0,48<sup><xref ref-type="table-fn" rid="TFN12">&#8224;</xref></sup></td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN11">
              <label>(*)</label>
              <p>Teste exato de Fisher (bicaudado);</p>
            </fn>
            <fn id="TFN12">
              <label>(&#8224;)</label>
              <p>Teste de Mann-Whitney (bicaudado); PVC: press&#227;o venosa central; DPOC: doen&#231;a pulmonar obstrutiva cr&#244;nica; IAM: infarto agudo do mioc&#225;rdio; DVE: disfun&#231;&#227;o ventricular esquerda; FE: fra&#231;&#227;o de eje&#231;&#227;o; RFG: ritmo de filtra&#231;&#227;o glomerular; CV: coeficiente de varia&#231;&#227;o.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>No per&#237;odo de 48-72 horas de PO, houve diferen&#231;a estat&#237;stica entre os grupos quanto &#224; incid&#234;ncia de FA (<xref ref-type="table" rid="t7">Tabela 3</xref>). Em G15, 8,56% dos pacientes desenvolveram FA, em contraste com 22,86% daqueles no G20 (p = 0,03). A RRA foi de 14,28% [intervalo de confian&#231;a de 95% (IC 95%): 2,14-26,28], e RRR de 62,50% (IC 95%: 9,79-84,41) e NNT igual a 7. O poder da amostra foi de 64,40%.</p>
        <table-wrap id="t7">
          <label>Tabela 3</label>
          <caption>
            <title>Compara&#231;&#227;o de fibrila&#231;&#227;o atrial em 72 horas de p&#243;s-operat&#243;rio, &#243;bito hospitalar, tempo de internamento ap&#243;s revasculariza&#231;&#227;o do mioc&#225;rdio, n&#250;mero de enxertos e uso de circula&#231;&#227;o extracorp&#243;rea entre pacientes com controle de PVC &#8804; 15 cmH<sub>2</sub>O (G15) e PVC &#8804; 20 cmH<sub>2</sub>O (G20)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Vari&#225;vel</th>
                <th align="center">G15 (n = 70)</th>
                <th align="center">G20 (n = 70)</th>
                <th align="center">p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Fibrila&#231;&#227;o atrial, n (%)</td>
                <td align="center">6 (8,57)</td>
                <td align="center">16 (22,86)</td>
                <td align="center">0,03<xref ref-type="table-fn" rid="TFN13">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">&#211;bito hospitalar, n (%)</td>
                <td align="center">4 (5,71)</td>
                <td align="center">8 (11,42)</td>
                <td align="center">0,07<xref ref-type="table-fn" rid="TFN13">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">Dias de internamento, m&#233;dia (CV)</td>
                <td align="center">7,14 (0,70)</td>
                <td align="center">8,21 (0,68)</td>
                <td align="center">0,36<sup><xref ref-type="table-fn" rid="TFN14">&#8224;</xref></sup></td>
              </tr>
              <tr>
                <td align="left">Enxertos, mediana</td>
                <td align="center">3</td>
                <td align="center">2</td>
                <td align="center">0,22 <sup><xref ref-type="table-fn" rid="TFN14">&#8224;</xref></sup></td>
              </tr>
              <tr>
                <td align="left">Circula&#231;&#227;o extracorp&#243;rea, n (%)</td>
                <td align="center">47 (67,10)</td>
                <td align="center">39 (55,70)</td>
                <td align="center">0,22<xref ref-type="table-fn" rid="TFN13">*</xref>
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN13">
              <label>(*)</label>
              <p>Teste exato de Fisher (bicaudado);</p>
            </fn>
            <fn id="TFN14">
              <label>(&#8224;)</label>
              <p>Teste de Mann-Whitney (bicaudado); PVC: press&#227;o venosa central; CV: coeficiente de varia&#231;&#227;o.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Ocorreram 4 &#243;bitos hospitalares no G15, sendo 2 por sepse pulmonar e 2 por AVC. No G20, foram 8 &#243;bitos hospitalares, sendo 5 por AVC, 2 por sepse pulmonar e 1 por sepse urin&#225;ria. N&#227;o houve diferen&#231;a estat&#237;stica na mortalidade (p = 0,07). Tamb&#233;m n&#227;o houve diferen&#231;a em rela&#231;&#227;o a n&#250;mero de enxertos, uso de CEC e dias de internamento no PO.</p>
        <p>Foram agrupados todos os pacientes que desenvolveram FA e analisadas as vari&#225;veis com rela&#231;&#227;o a mortalidade, tempo de internamento, uso de CEC e n&#250;mero de enxertos (<xref ref-type="table" rid="t8">Tabela 4</xref>). A idade foi estatisticamente significativa entre os grupos (p = 0,04), com m&#233;dia de 65,68 anos entre aqueles que desenvolveram FA e 60,73 nos pacientes sem FA. O tempo de internamento mostrou-se significativo (p = 0,0012) entre os pacientes com FA, com m&#233;dia de 10,22 dias (CV = 0,70). As demais vari&#225;veis mostraram-se estatisticamente semelhantes.</p>
        <table-wrap id="t8">
          <label>Tabela 4</label>
          <caption>
            <title>Compara&#231;&#227;o de idade, mortalidade, tempo de internamento, n&#250;mero de enxertos e uso de circula&#231;&#227;o extracorp&#243;rea entre pacientes que desenvolveram fibrila&#231;&#227;o atrial (FA) e pacientes que n&#227;o desenvolveram FA</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Vari&#225;vel</th>
                <th align="center">Com FA (n = 22; 15,17%)</th>
                <th align="center">Sem FA (n = 118; 84,29%)</th>
                <th align="center">p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Idade, m&#233;dia (CV)</td>
                <td align="center">65,68 (0,15)</td>
                <td align="center">60,73 (0,16)</td>
                <td align="center">0,04</td>
              </tr>
              <tr>
                <td align="left">&#211;bito hospitalar, n (%)</td>
                <td align="center">2 (5,71%)</td>
                <td align="center">10 (11,42%)</td>
                <td align="center">1,00<xref ref-type="table-fn" rid="TFN15">*</xref>
								</td>
              </tr>
              <tr>
                <td align="left">Dias de internamento, m&#233;dia (CV)</td>
                <td align="center">10,22 (0,70)</td>
                <td align="center">7,20 (0,67)</td>
                <td align="center">0,001<sup><xref ref-type="table-fn" rid="TFN16">&#8224;</xref></sup></td>
              </tr>
              <tr>
                <td align="left">Enxertos, mediana</td>
                <td align="center">2</td>
                <td align="center">2</td>
                <td align="center">0,69<sup><xref ref-type="table-fn" rid="TFN16">&#8224;</xref></sup></td>
              </tr>
              <tr>
                <td align="left">Circula&#231;&#227;o extracorp&#243;rea, n (%)</td>
                <td align="center">12 (54,55)</td>
                <td align="center">74 (62,71)</td>
                <td align="center">0,48<xref ref-type="table-fn" rid="TFN15">*</xref>
								</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN15">
              <label>(*)</label>
              <p>Teste exato de Fisher (bicaudado);</p>
            </fn>
            <fn id="TFN16">
              <label>(&#8224;)</label>
              <p>Teste de Mann-Whitney (bicaudado); CV: coeficiente de Varia&#231;&#227;o.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Este estudo comparou a incid&#234;ncia de FA nas primeiras 72 horas de PO de RM usando duas estrat&#233;gias de controle de PVC, com base na inten&#231;&#227;o de tratar, ou seja, o uso de diur&#233;tico teve por objetivo manter a PVC abaixo dos limites de corte. Pacientes com a estrat&#233;gia de manter a PVC menor ou igual a 15 cmH<sub>2</sub>O, nesse per&#237;odo, apresentaram menor incid&#234;ncia de FA se comparados aos pacientes que mantiveram controle da PVC menor ou igual a 20 cmH<sub>2</sub>O (8,56% vs. 22,86%; p = 0,03). Medidas de tamanho de efeito mostraram-se relevantes: a RRA do grupo G15 foi de 12,12%, equivalendo a um NNT de 7, ou seja, 1 a cada 7 pacientes se beneficiou do controle da PVC menor ou igual a 15 no PO de RM, sugerindo que manter essa medida controlada de PVC pode ser efetiva na redu&#231;&#227;o da incid&#234;ncia da arritmia. A incid&#234;ncia de FA em ambos os grupos separadamente, assim como a incid&#234;ncia de FA em toda a amostra (15,71%), assemelham-se &#224;s documentadas na literatura (5-40%).<xref ref-type="bibr" rid="B4">4</xref> A PVC foi medida com monitor em mmHg e em coluna de &#225;gua; optou-se por usar a medida em coluna de &#225;gua tendo em vista que alguns pacientes permaneceram apenas 24 horas com a monitoriza&#231;&#227;o em mmHg. Nos pacientes est&#225;veis ap&#243;s 24 horas, &#233; rotina do servi&#231;o retirar a monitoriza&#231;&#227;o de press&#227;o arterial invasiva, passando a PVC a ser controlada s&#243; em coluna de &#225;gua.</p>
        <p>A FA no PO eleva o risco de AVC isqu&#234;mico, taquicardia ventricular, fibrila&#231;&#227;o ventricular, hipotens&#227;o e insufici&#234;ncia card&#237;aca.<xref ref-type="bibr" rid="B3">3</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> A FA em PO de RM est&#225; associada ao aumento do tempo de internamento PO e aumento da mortalidade hospitalar.<xref ref-type="bibr" rid="B6">6</xref> Sobral et al.<xref ref-type="bibr" rid="B9">9</xref> revelaram que o tempo de internamento entre os pacientes com FA foi maior (m&#233;dia de 16,4 dias; p = 0,004), contudo n&#227;o estabeleceram se a FA foi a causa da hospitaliza&#231;&#227;o prolongada ou se um indicativo de gravidade em pacientes mais cr&#237;ticos; mostraram ainda um pico de incid&#234;ncia m&#233;dia de 2,6 dias (mediana de 2 dias). Da Silva et al.<xref ref-type="bibr" rid="B10">10</xref> mostraram que a m&#233;dia de internamento em pacientes que desenvolveram FA ap&#243;s cirurgia card&#237;aca foi de 16,9 dias (p = 0,001). Nessa amostra, o tempo de internamento mostrou-se significativamente maior nos pacientes com FA (p = 0,0012). N&#227;o foi avaliado o pico de incid&#234;ncia em rela&#231;&#227;o ao tempo, por&#233;m o per&#237;odo que compreende o estudo da amostra (72 horas) est&#225; dentro do tempo previsto, conforme a literatura, para maior incid&#234;ncia dessa arritmia.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> A taxa de mortalidade encontrada por Sobral et al.<xref ref-type="bibr" rid="B9">9</xref> em 1 ano de PO foi de 4,7% (n = 109; p = 0,001) para pacientes que desenvolveram FA, com taxa de reinternamento em 30 dias de 7,6% (n = 168; p = 0,004) e reinternamento em 1 ano de 18,7% (n = 417; p = 0,004). Nesta amostra foram avaliados a mortalidade hospitalar e o tempo de internamento, tendo sido ligeiramente maiores no G20, mas sem diferen&#231;a estat&#237;stica.</p>
        <p>O conhecimento dos fatores de risco que levam &#224; FA no PO de RM tem grande import&#226;ncia. Possibilita a utiliza&#231;&#227;o de medidas profil&#225;ticas, com o intuito de reduzir a incid&#234;ncia dessa arritmia, assim como de suas complica&#231;&#245;es.<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>
				</p>
        <p>Alguns fatores de risco para desenvolvimento de FA foram demonstrados na literatura. A idade acima de 65 anos<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref> &#233; descrita como um dos fatores de risco mais importantes.<xref ref-type="bibr" rid="B7">7</xref><sup>-</sup><xref ref-type="bibr" rid="B12">12</xref> A idade est&#225; associada a altera&#231;&#245;es na estrutura do mioc&#225;rdio por processos degenerativos (fibrose e dilata&#231;&#227;o), que provocam aus&#234;ncia de per&#237;odo refrat&#225;rio efetivo, dispers&#227;o da refratariedade e da condu&#231;&#227;o e automaticidade anormal.<xref ref-type="bibr" rid="B4">4</xref><sup>-</sup><xref ref-type="bibr" rid="B7">7</xref> A idade avan&#231;ada tamb&#233;m est&#225; relacionada a aumento da mortalidade hospitalar.<xref ref-type="bibr" rid="B9">9</xref> Em nosso estudo, a m&#233;dia de idade foi de 60 anos no G15 e de 63 anos no G20, n&#227;o havendo diferen&#231;a estat&#237;stica (p = 0,07). A idade foi significativa na an&#225;lise entre os pacientes que desenvolveram FA em rela&#231;&#227;o &#224;queles que n&#227;o desenvolveram FA (p = 0,04). O grupo que desenvolveu FA teve m&#233;dia de aproximadamente 66 anos, resultado semelhante ao encontrado na literatura.<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>
				</p>
        <p>Diabetes mellitus leva a altera&#231;&#245;es metab&#243;licas, como aumento do estresse oxidativo, eleva&#231;&#227;o dos n&#237;veis de &#225;cidos graxos livres e inflama&#231;&#227;o tecidual cr&#244;nica. Essas altera&#231;&#245;es resultam em mudan&#231;as na estrutura e na condu&#231;&#227;o el&#233;trica dos &#225;trios e contribui para o desenvolvimento de FA no PO.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Nesta amostra, a preval&#234;ncia de diabetes mellitus foi semelhante entre os grupos (p = 0,07).</p>
        <p>A doen&#231;a arterial obstrutiva perif&#233;rica associa-se &#224; gravidade do perfil cl&#237;nico do paciente e &#224;s comorbidades que predisp&#245;em ao aparecimento da FA em PO de cirurgia card&#237;aca.<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref> O estudo de El-Chami et al.<xref ref-type="bibr" rid="B14">14</xref> identificou a arteriopatia perif&#233;rica como um dos fatores de risco para FA, considerando-a preditor independente para mortalidade. Em nosso estudo, a preval&#234;ncia de doen&#231;a arterial obstrutiva perif&#233;rica apresentou semelhan&#231;a estat&#237;stica entre os grupos.</p>
        <p>Outras condi&#231;&#245;es associadas ao desenvolvimento de FA no PO de RM s&#227;o DPOC,<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref> insufici&#234;ncia renal cr&#244;nica,<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> IAM pr&#233;vio<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref> e disfun&#231;&#227;o ventricular esquerda.<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> Esses fatores de risco tiveram preval&#234;ncia semelhante entre os dois grupos.</p>
        <p>A quantidade de enxertos realizados durante a cirurgia e a utiliza&#231;&#227;o de CEC s&#227;o tamb&#233;m apontadas como fatores de risco,<xref ref-type="bibr" rid="B7">7</xref> por&#233;m com algum grau de diverg&#234;ncia entre diferentes autores.<xref ref-type="bibr" rid="B9">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref><sup>-</sup><xref ref-type="bibr" rid="B19">19</xref> A CEC &#233; uma t&#233;cnica invasiva e est&#225; relacionada &#224; isquemia atrial e ao desencadeamento da resposta inflamat&#243;ria no PO de cirurgias card&#237;acas.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B20">20</xref> N&#227;o foram encontradas diferen&#231;as estat&#237;sticas entre os grupos de estudo em rela&#231;&#227;o a esses par&#226;metros.</p>
        <p>Algumas estrat&#233;gias de preven&#231;&#227;o da FA no PO de RM foram desenvolvidas, especialmente por meio da profilaxia farmacol&#243;gica. Os betabloqueadores s&#227;o os f&#225;rmacos de escolha, pois reduzem significativamente a incid&#234;ncia de FA e est&#227;o relacionados com menor morbimortalidade PO.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref> &#201; a classe farmacol&#243;gica mais estudada e utilizada com essa finalidade, especialmente pelo controle que exerce sobre o aumento do t&#244;nus simp&#225;tico em pacientes submetidos a cirurgia card&#237;aca.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> O uso de betabloqueadores est&#225; indicado para todos os pacientes submetidos a RM, exceto se houver contraindica&#231;&#245;es.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B21">21</xref> A profilaxia com amiodarona e magn&#233;sio endovenoso &#233; recomendada quando h&#225; contraindica&#231;&#227;o ao uso de betabloqueadores.<xref ref-type="bibr" rid="B22">22</xref> Em estudos mais antigos, o uso de estatinas no pr&#233;-operat&#243;rio e PO era considerado relevante para a preven&#231;&#227;o de FA ap&#243;s RM. A a&#231;&#227;o desses f&#225;rmacos consiste em diminuir a inflama&#231;&#227;o de pacientes com doen&#231;a arterial coronariana. Em uma meta-an&#225;lise, Zheng et al.<xref ref-type="bibr" rid="B23">23</xref> demonstraram que a terapia com estatina reduziu significativamente a incid&#234;ncia de FA e o tempo de perman&#234;ncia no hospital. O estudo de Bockeria et al.<xref ref-type="bibr" rid="B24">24</xref> demonstrou que pacientes que receberam estatina antes da cirurgia de RM tiveram maiores benef&#237;cios na preven&#231;&#227;o de FA precoce do que os que n&#227;o receberam. Por&#233;m, ainda h&#225; controv&#233;rsias na literatura. Em uma meta-an&#225;lise recente,<xref ref-type="bibr" rid="B25">25</xref> os autores conclu&#237;ram que a terapia com estatina no PO n&#227;o previne a FA em pacientes submetidos a cirurgia card&#237;aca eletiva. Em nosso servi&#231;o, o uso de betabloqueadores e estatinas mant&#233;m-se no pr&#233;-operat&#243;rio e &#233; reintroduzido com a dieta em geral no primeiro dia de PO. Se o paciente estiver em uso de dobutamina ou noradrenalina, o betabloqueador &#233; introduzido ap&#243;s suspens&#227;o do f&#225;rmaco vasoativo.</p>
        <p>A PVC &#233; um importante preditor de mortalidade precoce, independente do d&#233;bito card&#237;aco e de outras condi&#231;&#245;es cl&#237;nicas vari&#225;veis, principalmente nas primeiras 6 horas de PO, devido &#224; instabilidade hemodin&#226;mica.<xref ref-type="bibr" rid="B26">26</xref> O objetivo do controle rigoroso da PVC &#233; mensurar a press&#227;o &#224; qual os &#225;trios s&#227;o submetidos, levando em conta o volume intravascular. O resultado da sobrecarga volum&#233;trica intravascular &#233; a hipertens&#227;o, dilata&#231;&#227;o e redu&#231;&#227;o da contra&#231;&#227;o atrial, devido ao estiramento das fibras musculares card&#237;acas. Por&#233;m, &#233; revers&#237;vel com a administra&#231;&#227;o de diur&#233;ticos.<xref ref-type="bibr" rid="B26">26</xref><sup>-</sup><xref ref-type="bibr" rid="B28">28</xref> Kalus et al.<xref ref-type="bibr" rid="B29">29</xref> demonstraram que o controle hemodin&#226;mico baseado na administra&#231;&#227;o de grandes quantidades de fluidos &#233; respons&#225;vel pelo aumento da press&#227;o intra-atrial e pode representar um fator desencadeante de FA no PO de cirurgia cardiotor&#225;cica. Observaram que os pacientes de cirurgia cardiotor&#225;cica que desenvolveram FA receberam aproximadamente 1 litro de fluidos a mais que aqueles que n&#227;o desenvolveram a arritmia, sendo essa diferen&#231;a mais significativa no segundo dia de PO (p = 0,04). O fator limitante para o estudo foi a falta de documenta&#231;&#227;o do aumento de press&#227;o e volume atrial ap&#243;s a cirurgia.</p>
        <p>A sobrecarga de volume intravascular provoca uma dispers&#227;o anormal do per&#237;odo refrat&#225;rio do &#225;trio, devido ao aumento de volume e press&#227;o intra-atrial. Dessa forma, o &#225;trio torna-se mais vulner&#225;vel ao desenvolvimento de FA.<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B30">30</xref><sup>,</sup><xref ref-type="bibr" rid="B31">31</xref> O estudo de Hwang et al.<xref ref-type="bibr" rid="B31">31</xref> sugeriu que o volume intravascular &#233; um importante par&#226;metro, assim como a gasometria arterial, a hemoglobina e o pot&#225;ssio s&#233;rico, a serem verificados quando h&#225; FA em PO de RM, pois pode esclarecer as causas revers&#237;veis dessa arritmia. Silva et al.<xref ref-type="bibr" rid="B10">10</xref> demonstraram que o excesso de balan&#231;o h&#237;drico nas primeiras 24 horas de PO &#233; tamb&#233;m um fator de risco para a FA ap&#243;s RM. Os autores relacionaram a congest&#227;o pulmonar como fator desencadeante de arritmia. No estudo de Koletsis et al.<xref ref-type="bibr" rid="B15">15</xref>, houve rela&#231;&#227;o entre o balan&#231;o h&#237;drico positivo, refletindo o excesso de volume intravascular, e a ocorr&#234;ncia de FA em PO de RM. O balan&#231;o h&#237;drico positivo tamb&#233;m foi apontado como respons&#225;vel pelo aumento da press&#227;o atrial esquerda e da congest&#227;o pulmonar, levando &#224; hip&#243;xia.</p>
        <p>O aumento do volume atrial esquerdo identificado na fase pr&#233;-operat&#243;ria predisp&#245;e ao desenvolvimento de FA ap&#243;s cirurgia card&#237;aca. Wang et al.<xref ref-type="bibr" rid="B32">32</xref> demonstraram que o &#237;ndice de expans&#227;o do &#225;trio esquerdo foi associado com mortalidade intra-hospitalar e FA no PO de RM, sendo um fator de risco independente. Osranek et al.<xref ref-type="bibr" rid="B16">16</xref> encontraram que o aumento acima de 32 ml/m<sup>2</sup> no volume ventricular esquerdo aumenta em 5 vezes o risco de desenvolver FA, como um fator independente de idade e outros par&#226;metros cir&#250;rgicos. Patel et al.<xref ref-type="bibr" rid="B33">33</xref> encontraram que a cada 5 mm de aumento do &#225;trio esquerdo, visto por meio do ecocardiograma, aumenta o risco de FA em 39%. Sanfilippo et al.<xref ref-type="bibr" rid="B30">30</xref> chegaram &#224; conclus&#227;o de que a manuten&#231;&#227;o do ritmo sinusal previne a progress&#227;o da hipertrofia do &#225;trio esquerdo e previne seus efeitos adversos. Maceira et al.<xref ref-type="bibr" rid="B34">34</xref> estudaram as dimens&#245;es do &#225;trio direito por meio da resson&#226;ncia nuclear magn&#233;tica. Os melhores indicadores independentes de aumento de volume atrial foram a &#225;rea maior que 16 cm<sup>2</sup>/m<sup>2</sup> e o di&#226;metro longitudinal maior que 3,5 cm/m<sup>2</sup>. O presente estudo n&#227;o avaliou o volume atrial esquerdo na fase pr&#233;-operat&#243;ria, pois nem todos os pacientes foram submetidos ao exame ecocardiogr&#225;fico antes da cirurgia.</p>
        <p>Nesta s&#233;rie, o controle da PVC abaixo de 15 cmH<sub>2</sub>O demonstrou import&#226;ncia para a preven&#231;&#227;o do desenvolvimento de FA ap&#243;s RM, comparado com o controle abaixo de 20 cmH<sub>2</sub>O. Obteve-se um poder estat&#237;stico da amostra satisfat&#243;rio, com 66,70%; contudo, h&#225; necessidade de mais estudos, com maiores amostras, para autenticar essa conduta como medida profil&#225;tica para a FA no PO de cirurgia card&#237;aca. Os dados presentes neste estudo sugerem que h&#225; vantagem em se fazer um controle mais rigoroso da PVC, a fim de evitar sobrecargas volum&#233;tricas excessivas. N&#227;o foi avaliada a mortalidade ap&#243;s alta, nem o aparecimento de FA ap&#243;s esse per&#237;odo. Em outro estudo j&#225; publicado,<xref ref-type="bibr" rid="B35">35</xref> estes autores demonstraram que manter o controle rigoroso da PVC pode prevenir FA ap&#243;s RM, comparado com o grupo controle sem o controle da PVC. A estrat&#233;gia mostrou-se muito ben&#233;fica (NNT = 7) nesta amostra relativamente pequena (140 pacientes) em estudo de um &#250;nico centro.</p>
        <p>Estudos com maior n&#250;mero de pacientes e multic&#234;ntrico, com poder de avaliar n&#227;o s&#243; incid&#234;ncia de FA, mas tamb&#233;m mortalidade e aumento de custos com maior tempo de internamento, s&#227;o necess&#225;rios para melhor avaliar essa modalidade de tratamento. Por outro lado, vale ressaltar que n&#227;o houve nenhum preju&#237;zo para os pacientes com uso de diur&#233;tico, n&#227;o houve aumento de insufici&#234;ncia renal ou instabilidade hemodin&#226;mica, al&#233;m de se tratar de estrat&#233;gia de baix&#237;ssimo custo. Sendo assim, o controle da PVC pode servir como m&#233;todo complementar na profilaxia da FA no PO de RM.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>O controle da PVC como meta abaixo de 15 cmH<sub>2</sub>O, mantido nas primeiras 48-72 horas de PO, &#233; capaz de reduzir a incid&#234;ncia de FA no PO de RM. A cada 7 pacientes, 1 se beneficia dessa estrat&#233;gia.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
