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  <front>
    <journal-meta>
      <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-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">cCvQppRNKTKxVgRTwX3Tw6J</article-id>
      <article-id pub-id-type="other">00002</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2004001400002</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(04)08300202</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2004001400002</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Fatores de risco e morbimortalidade associados &#224; fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Rog&#233;rio Gomes da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lima</surname>
            <given-names>Gustavo Glotz de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Laranjeira</surname>
            <given-names>Andr&#233;ia</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Costa</surname>
            <given-names>Altamiro Reis da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Edemar</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues</surname>
            <given-names>Rubem</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Funda&#231;&#227;o Universit&#225;ria de Cardiologia</institution>
        <institution content-type="orgdiv1">Instituto de Cardiologia do Rio Grande do Sul </institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2004</year>
      </pub-date>
      <volume>83</volume>
      <issue>2</issue>
      <fpage>99</fpage>
      <lpage>104</lpage>
      <history>
        <date date-type="accepted">
          <day>06</day>
          <month>01</month>
          <year>2004</year>
        </date>
        <date date-type="received">
          <day>11</day>
          <month>07</month>
          <year>2003</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>OBJETIVO: Determinar a incid&#234;ncia de fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca, seu impacto sobre a morbimortalidade e o tempo de interna&#231;&#227;o hospitalar e analisar os fatores de risco presentes no pr&#233;, trans e p&#243;s-operat&#243;rio. M&#201;TODO: Estudo de coorte contempor&#226;neo com 158 pacientes adultos submetidos &#224; cirurgia card&#237;aca, sendo exclu&#237;dos aqueles com fibrila&#231;&#227;o atrial no pr&#233;-operat&#243;rio. Os pacientes foram avaliados por monitoriza&#231;&#227;o card&#237;aca cont&#237;nua e eletrocardiogramas di&#225;rios e a fibrila&#231;&#227;o atrial considerada como qualquer epis&#243;dio de ritmo irregular, com presen&#231;a de ondas f de morfologia e amplitude vari&#225;veis. RESULTADOS: A incid&#234;ncia de fibrila&#231;&#227;o atrial foi de 28,5%, sendo 21,6% para os pacientes revascularizados e 44,3% para os submetidos &#224; corre&#231;&#227;o valvar. Fatores independentemente associados &#224; fibrila&#231;&#227;o atrial foram insufici&#234;ncia card&#237;aca esquerda no pr&#233;-operat&#243;rio (p=0,05; RC=2,2), balan&#231;o h&#237;drico total (p=0,01; RC=1,0), tempo de cirurgia (p=0,03; RC=1,01) e outros fatores associados: idade &gt; 70 anos, doen&#231;a valvar a&#243;rtica, agita&#231;&#227;o psicomotora, tempo de perman&#234;ncia de drenos, congest&#227;o pulmonar e insufici&#234;ncia respirat&#243;ria no p&#243;s-operat&#243;rio. O uso de betabloqueadores (p=0,01; RC=0,3) foi um fator de prote&#231;&#227;o. Fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria associou-se a aumento do tempo de interna&#231;&#227;o hospitalar (16,9 &#177; 12,3 dias vs 9,2 &#177; 4,0 dias, p&lt;0,001) e a maior incid&#234;ncia de acidente vascular cerebral ou &#243;bito p&#243;s-operat&#243;rio, (p=0,02). CONCLUS&#195;O: A incid&#234;ncia de fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca foi elevada e ocasionou significativo aumento de morbimortalidade e tempo de interna&#231;&#227;o hospitalar. Entre os fatores de risco independentes destaca-se o balan&#231;o h&#237;drico excessivo e, como fator protetor, uso de betabloqueadores.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>fibrila&#231;&#227;o atrial</kwd>
        <kwd>arritmias</kwd>
        <kwd>cirurgia card&#237;aca</kwd>
        <kwd>cuidados p&#243;s-operat&#243;rio</kwd>
        <kwd>fatores de risco</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>17</day>
        <month>08</month>
        <year>2004</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>Fatores de risco e morbimortalidade associados &#224; fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca  </p>
    <p>Rog&#233;rio Gomes da Silva; Gustavo Glotz de Lima; Andr&#233;ia Laranjeira; Altamiro Reis da Costa; Edemar Pereira; Rubem Rodrigues </p>
    <p> Porto Alegre, RS   </p>
    <p>Instituto de Cardiologia do Rio Grande do Sul/Funda&#231;&#227;o Universit&#225;ria de Cardiologia </p>
    <p>
      <xref ref-type="corresp" rid="end">Endere&#231;o para correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>OBJETIVO: </bold>Determinar a incid&#234;ncia de fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca, seu impacto sobre a morbimortalidade e o tempo de interna&#231;&#227;o hospitalar e analisar os fatores de risco presentes no pr&#233;, trans e p&#243;s-operat&#243;rio. </p>
    <p><bold>M&#201;TODO: </bold>Estudo de coorte contempor&#226;neo com 158 pacientes adultos submetidos &#224; cirurgia card&#237;aca, sendo exclu&#237;dos aqueles com fibrila&#231;&#227;o atrial no pr&#233;-operat&#243;rio. Os pacientes foram avaliados por monitoriza&#231;&#227;o card&#237;aca cont&#237;nua e eletrocardiogramas di&#225;rios e a fibrila&#231;&#227;o atrial considerada como qualquer epis&#243;dio de ritmo irregular, com presen&#231;a de ondas f de morfologia e amplitude vari&#225;veis. </p>
    <p><bold>RESULTADOS: </bold>A incid&#234;ncia de fibrila&#231;&#227;o atrial foi de 28,5%, sendo 21,6% para os pacientes revascularizados e 44,3% para os submetidos &#224; corre&#231;&#227;o valvar. Fatores independentemente associados &#224; fibrila&#231;&#227;o atrial foram insufici&#234;ncia card&#237;aca esquerda no pr&#233;-operat&#243;rio (p=0,05; RC=2,2), balan&#231;o h&#237;drico total (p=0,01; RC=1,0), tempo de cirurgia (p=0,03; RC=1,01) e outros fatores associados: idade &gt; 70 anos, doen&#231;a valvar a&#243;rtica, agita&#231;&#227;o psicomotora, tempo de perman&#234;ncia de drenos, congest&#227;o pulmonar e insufici&#234;ncia respirat&#243;ria no p&#243;s-operat&#243;rio. O uso de betabloqueadores (p=0,01; RC=0,3) foi um fator de prote&#231;&#227;o. Fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria associou-se a aumento do tempo de interna&#231;&#227;o hospitalar (16,9 &#177; 12,3 dias vs 9,2 &#177; 4,0 dias, p&lt;0,001) e a maior incid&#234;ncia de acidente vascular cerebral ou &#243;bito p&#243;s-operat&#243;rio, (p=0,02). </p>
    <p><bold>CONCLUS&#195;O: </bold>A incid&#234;ncia de fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca foi elevada e ocasionou significativo aumento de morbimortalidade e tempo de interna&#231;&#227;o hospitalar. Entre os fatores de risco independentes destaca-se o balan&#231;o h&#237;drico excessivo e, como fator protetor, uso de betabloqueadores.  </p>
    <p><bold>Palavras-chave:</bold> fibrila&#231;&#227;o atrial, arritmias, cirurgia card&#237;aca, cuidados p&#243;s-operat&#243;rio, fatores de risco</p>
    <p>As arritmias atriais s&#227;o comuns no p&#243;s-operat&#243;rio de cirurgia cardiotor&#225;cica. Ocorrem em 11% a 40% dos pacientes ap&#243;s cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica e em aproximadamente 50% dos submetidos &#224; cirurgia valvar<sup>1,2</sup>. A fibrila&#231;&#227;o atrial &#233; a arritmia mais comum ap&#243;s cirurgia card&#237;aca<sup>3</sup>. Comumente, &#233; uma condi&#231;&#227;o auto-limitada, raramente causando morte perioperat&#243;ria, mas podendo prolongar o per&#237;odo de interna&#231;&#227;o hospitalar, aumentando os custos. Algumas vezes pode ser considerada causa de infarto agudo do mioc&#225;rdio perioperat&#243;rio e de fen&#244;menos tromboemb&#243;licos<sup>3,4</sup>. Fatores de risco est&#227;o associados &#224; fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca, tais como insufici&#234;ncia card&#237;aca esquerda, s&#237;ndrome de resposta inflamat&#243;ria sist&#234;mica, septicemia ou fal&#234;ncia de m&#250;ltiplos &#243;rg&#227;os<sup>5</sup>, suspens&#227;o de betabloqueadores<sup>6</sup>, doen&#231;a pulmonar obstrutiva cr&#244;nica<sup>7 </sup>e necessidade de suporte ventilat&#243;rio mec&#226;nico<sup>8</sup>, mas &#233; a idade avan&#231;ada o fator de risco mais associado<sup>9</sup>. Nos pacientes com maior risco, &#233; importante considerar medidas de preven&#231;&#227;o<sup>10</sup>.  </p>
    <p>Este estudo prospectivo e observacional tem como objetivo avaliar a incid&#234;ncia e os fatores de risco pr&#233;, trans e p&#243;s-operat&#243;rios associados &#224; fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca, em um centro de refer&#234;ncia cardiol&#243;gica nacional, e analisar a morbimortalidade e o tempo de interna&#231;&#227;o hospitalar relacionado-os com esta arritmia.  </p>
    <p>
      <bold>M&#233;todo</bold>
    </p>
    <p>Entre janeiro e maio de 2002, 158 pacientes submetidos &#224; cirurgia card&#237;aca foram selecionados na fase de p&#243;s-operat&#243;rio imediato, em uma Institui&#231;&#227;o de refer&#234;ncia.  </p>
    <p>A amostra compreendeu pacientes selecionados sistematicamente, submetidos &#224; cirurgia card&#237;aca em um determinado dia da semana, sendo que, a cada semana, o dia da sele&#231;&#227;o era diferente, consecutivamente, de segunda &#224; sexta-feira. Todos os pacientes arrolados durante o estudo foram acompanhados at&#233; o dia da alta, n&#227;o tendo sido perdido durante o acompanhamento nenhum paciente ou informa&#231;&#227;o do protocolo. A m&#233;dia de sele&#231;&#227;o foi de 31,8 pacientes/m&#234;s.  </p>
    <p>Trata-se de um estudo de coorte contempor&#226;neo, no qual os pacientes foram avaliados em quatro momentos distintos: no p&#243;s-operat&#243;rio imediato; no centro de terapia intensiva (CTI p&#243;s-operat&#243;rio); na alta do CTI p&#243;s-operat&#243;rio e na alta hospitalar.  </p>
    <p>Foram inclu&#237;dos no trabalho pacientes submetidos &#224; cirurgia card&#237;aca com ou sem circula&#231;&#227;o extracorp&#243;rea, devido &#224; cardiopatia isqu&#234;mica ou valvar e, exclu&#237;dos os com hist&#243;ria de fibrila&#231;&#227;o atrial no pr&#233;-operat&#243;rio.  </p>
    <p>Em cada uma das quatro fases de avalia&#231;&#227;o foi usado um protocolo previamente aprovado pelo Comit&#234; de &#201;tica em Pesquisa, com os dados a serem pesquisados e o termo de consentimento informado. Na fase de sele&#231;&#227;o, os dados demogr&#225;ficos e pr&#233;-operat&#243;rios foram levantados.  </p>
    <p>Todos os pacientes foram examinados pessoalmente pelo autor, que analisou tamb&#233;m exames pr&#233; e p&#243;s-operat&#243;rios. Na fase de CTI - p&#243;s-operat&#243;rio e na fase de alta da CTI, os pacientes foram avaliados diariamente do ponto de vista cl&#237;nico e laboratorial.  </p>
    <p>O ritmo card&#237;aco foi avaliado por meio de monitoriza&#231;&#227;o card&#237;aca cont&#237;nua em todos os pacientes durante um per&#237;odo m&#237;nimo de 72h (fase de CTI p&#243;s-operat&#243;rio) e por exames eletrocardiogr&#225;ficos di&#225;rios at&#233; a alta hospitalar. Eletrocardiogramas adicionais eram realizados quando os pacientes referiam palpita&#231;&#245;es, taquicardia ou angina e exames p&#243;s-operat&#243;rios bioqu&#237;micos, hematol&#243;gicos e radiol&#243;gicos, de acordo com a rotina de servi&#231;o de p&#243;s-operat&#243;rio da Institui&#231;&#227;o.  </p>
    <p>Foi considerada fibrila&#231;&#227;o atrial (desfecho prim&#225;rio) qualquer epis&#243;dio de arritmia supraventricular cujo tra&#231;ado eletrocardiogr&#225;fico apresentasse ondas f de morfologia e amplitude vari&#225;veis, com ritmo ventricular irregular.  </p>
    <p>Foram admitidos para o trabalho epis&#243;dios de fibrila&#231;&#227;o atrial com dura&#231;&#227;o m&#237;nima de 15min ou que necessitassem de tratamento devido &#224; sintomatologia ou instabiliza&#231;&#227;o hemodin&#226;mica. Foi considerado uso de vasopressor, se feita infus&#227;o acima de 5&#181;g/Kg/min, al&#233;m das primeiras 2h de p&#243;s-operat&#243;rio.  </p>
    <p>Anemia p&#243;s-operat&#243;ria foi definida como hemat&#243;crito abaixo de 30% e/ou hemoglobina abaixo de 10mg/dl, ou se tivesse havido transfus&#227;o de ao menos uma unidade de concentrado de hem&#225;cias e hipocalemia, como n&#237;vel de pot&#225;ssio s&#233;rico abaixo de 3,5mmol/l.  </p>
    <p>Inicialmente, foram geradas tabelas de freq&#252;&#234;ncia para todas as vari&#225;veis contidas no banco de dados. Em seguida calculou-se a m&#233;dia &#177; desvio padr&#227;o para as vari&#225;veis quantitativas e o percentual para as qualitativas. Mediu-se a for&#231;a de associa&#231;&#227;o de cada um dos fatores para fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria atrav&#233;s de estimativas de risco relativo com intervalos de confian&#231;a de 95%. A signific&#226;ncia dessas associa&#231;&#245;es foi determinada pelo teste do qui-quadrado e, quando necess&#225;rio, pelo teste exato de Fischer. Compara&#231;&#245;es de dados quantitativos entre os grupos foram realizadas por teste t de Student para amostras independentes.  </p>
    <p>Para estabelecer o melhor modelo de predi&#231;&#227;o e controlar o potencial efeito de confus&#227;o entre os fatores analisados e a ocorr&#234;ncia de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria, utilizou-se um modelo matem&#225;tico baseado na regress&#227;o log&#237;stica multivariada. Foram selecionadas para serem inclu&#237;das no modelo log&#237;stico, vari&#225;veis referidas como relevantes na literatura e aquelas que demonstraram forte associa&#231;&#227;o com o desfecho na an&#225;lise bivariada realizada. O n&#237;vel de signific&#226;ncia adotado foi de 0,05. A an&#225;lise de dados foi realizada com o aux&#237;lio do programa SPSS, vers&#227;o 8.0.  </p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>Em nossa amostra predominaram os homens (64%) e a doen&#231;a arterial coronariana (70%). Do total de pacientes, 61% eram hipertensos, 60% tabagistas, 58% encontravam-se com angina inst&#225;vel e 54% utilizavam betabloqueadores. A m&#233;dia de idade dos pacientes foi de 60,9 &#177; 11,2 anos.  </p>
    <p>A incid&#234;ncia geral de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria foi de 28,5% (45 casos). Dos 158 pacientes acompanhados, houve uma m&#233;dia de 9 casos de fibrila&#231;&#227;o atrial por m&#234;s.  </p>
    <p>Na <xref ref-type="table" rid="tab1">tabela I</xref> encontram-se as vari&#225;veis categ&#243;ricas pr&#233;-operat&#243;rias, as caracter&#237;sticas demogr&#225;ficas dos pacientes, submetidas &#224; an&#225;lise bivariada em rela&#231;&#227;o &#224; ocorr&#234;ncia de fibrila&#231;&#227;o atrial. Foram identificados quatro fatores de risco significativamente relacionados &#224; maior incid&#234;ncia de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria: doen&#231;a valvular a&#243;rtica (p=0,02), insufici&#234;ncia card&#237;aca esquerda no pr&#233;-operat&#243;rio (p=0,006), n&#227;o utiliza&#231;&#227;o pr&#233;via de betabloqueadores (p=0,02) e idade &gt;70 anos (p=0,03). Dos 20 casos de valvopatia mitral 9 apresentaram fibrila&#231;&#227;o atrial (45%; p=0,07). Infarto agudo do mioc&#225;rdio pr&#233;vio, crescimento de onda P &#224; eletrocardiografia, cirurgia de urg&#234;ncia, reopera&#231;&#227;o e angina inst&#225;vel n&#227;o se relacionaram com fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio. Doen&#231;a arterial coronariana teve rela&#231;&#227;o inversa com fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria.</p>
    <table-wrap id="tab1">
      <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt01.jpg"/></table-wrap>
    <p>Comparando-se pacientes submetidos a revasculariza&#231;&#227;o mioc&#225;rdica com os que realizaram cirurgias valvares, encontrou-se maior incid&#234;ncia de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria para os que se submeteram &#224; cirurgia valvar (p=0,008; RR=2,18; IC: 1,28-3,70).  </p>
    <p>A an&#225;lise bivariada para vari&#225;veis categ&#243;ricas p&#243;s-operat&#243;rias (<xref ref-type="table" rid="tab2">tab. II</xref>) identificou tr&#234;s fatores associados a fibrila&#231;&#227;o atrial. O mais significativo foi agita&#231;&#227;o psicomotora (p=0,008) na qual fibrila&#231;&#227;o atrial ocorreu em 9 de 15 pacientes. Insufici&#234;ncia respirat&#243;ria e congest&#227;o pulmonar tamb&#233;m foram significativas no nosso estudo. Atrito peric&#225;rdico, infarto agudo do mioc&#225;rdio perioperat&#243;rio e uso de dopamina n&#227;o mostraram ser fatores relacionados com fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria.</p>
    <table-wrap id="tab2">
      <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt02.jpg"/></table-wrap>
    <p>Em rela&#231;&#227;o &#224;s vari&#225;veis cont&#237;nuas, associadas com fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria, a an&#225;lise bivariada demonstrou que o tempo de perman&#234;ncia dos drenos aumentado &#233; um fator significativo (p=0,04). Os pacientes com maior incid&#234;ncia de fibrila&#231;&#227;o atrial exibiram balan&#231;os h&#237;dricos cristal&#243;ide, col&#243;ide e total, significativamente mais positivos do que aqueles que n&#227;o os apresentaram (p=0,03, 0,04 e 0,04 respectivamente). Tempo de circula&#231;&#227;o extracorp&#243;rea e tempo de isquemia n&#227;o foram significativos no presente estudo. N&#237;vel de pot&#225;ssio pr&#233;-operat&#243;rio n&#227;o determinou diferen&#231;as (p=0,07). As demais dosagens bioqu&#237;micas e de hematologia p&#243;s-operat&#243;rias n&#227;o foram estatisticamente significativas (pot&#225;ssio, creatinina, s&#243;dio, glicemia, hemat&#243;crito e hemoglobina s&#233;ricas) (<xref ref-type="table" rid="a02tab03">tab. III</xref>).</p>
    <p content-type="asset">
      <table-wrap id="a02tab03">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt03.jpg"/></table-wrap>
    </p>
    <p>A regress&#227;o log&#237;stica multivariada identificou quatro preditores estatisticamente independentes de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria. Como vari&#225;vel pr&#233;-operat&#243;ria, a insufici&#234;ncia card&#237;aca esquerda e, como vari&#225;vel transoperat&#243;ria significativamente independente, o tempo de cirurgia excessivo. Em rela&#231;&#227;o &#224;s vari&#225;veis p&#243;s-operat&#243;rias, insufici&#234;ncia respirat&#243;ria, com signific&#226;ncia estat&#237;stica lim&#237;trofe (p=0,07), mostrou uma associa&#231;&#227;o clinicamente importante com maior incid&#234;ncia de fibrila&#231;&#227;o atrial. O balan&#231;o h&#237;drico total excessivamente positivo tamb&#233;m foi fator de risco significativo para o desencadeamento desta arritmia (1% de risco adicional para cada mililitro acumulado acima do balan&#231;o h&#237;drico m&#233;dio). O uso de betabloqueadores constituiu um fator de prote&#231;&#227;o para o desenvolvimento de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria. Insufici&#234;ncia respirat&#243;ria (p=0,07) n&#227;o mostrou uma associa&#231;&#227;o clinicamente importante com uma maior incid&#234;ncia. (<xref ref-type="table" rid="tab4">tab. IV</xref>)</p>
    <table-wrap id="tab4">
      <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt04.jpg"/></table-wrap>
    <p>O per&#237;odo de in&#237;cio da fibrila&#231;&#227;o atrial encontra-se na <xref ref-type="fig" rid="fig1">figura 1</xref> onde &#233; observado que a maioria dos pacientes (63%) apresentou arritmia no 2&#186; (13 casos) e no 3&#186; dia (16 casos) de p&#243;s-operat&#243;rio; no 4&#186; dia de p&#243;s-operat&#243;rio 11% dos pacientes apresentaram fibrila&#231;&#227;o atrial e, no 5&#186; dia, 8%. Esta arritmia foi evidenciada em 39 pacientes (86,7%) durante o per&#237;odo de unidade de terapia intensiva (UTI), sendo que 79% apresentaram fibrila&#231;&#227;o atrial at&#233; o 3&#186; dia de perman&#234;ncia na UTI.</p>
    <fig id="fig1">
      <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf01.jpg"/></fig>
    <p>Todos os 45 casos de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria tiveram alta em ritmo sinusal. Dezoito (40%) casos reverteram para ritmo sinusal espontaneamente, antes de qualquer medida terap&#234;utica. A maioria dos pacientes analisada neste estudo foi tratada e revertida com amiodarona administrada por via intravenosa (40%). Oito dos casos de revers&#227;o espont&#226;nea receberam digital intravenoso para o controle da resposta ventricular. Foram submetidos &#224; cardiovers&#227;o el&#233;trica 9 pacientes: 4 por instabilidade hemodin&#226;mica, e os outros 5 tratados com amiodarona antes da cardiovers&#227;o el&#233;trica.  </p>
    <p>Dentre os pacientes que utilizaram betabloqueadores, tiveram menor incid&#234;ncia de fibrila&#231;&#227;o atrial (12,5%) os que receberam o medicamento no pr&#233; e p&#243;s-operat&#243;rio. Interromperam o uso de betabloqueador no p&#243;s-operat&#243;rio 61 pacientes, com incid&#234;ncia de fibrila&#231;&#227;o atrial de 23%. Os pacientes que n&#227;o utilizaram betabloqueadores no pr&#233; e no p&#243;s-operat&#243;rio, tiveram maior incid&#234;ncia de fibrila&#231;&#227;o atrial (39,7%) p=0,017. (<xref ref-type="fig" rid="fig2">fig. 2</xref>)</p>
    <fig id="fig2">
      <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf02.jpg"/></fig>
    <p>Marcada preven&#231;&#227;o de fibrila&#231;&#227;o atrial foi encontrada com o uso de betabloqueadores no pr&#233; e no p&#243;s-operat&#243;rio (p=0,028; RC=0,22; IC: 0,05-0,88), em rela&#231;&#227;o aos casos que n&#227;o utilizaram a droga. Houve ainda, preven&#231;&#227;o de fibrila&#231;&#227;o atrial nos pacientes que a utilizaram apenas no pr&#233;-operat&#243;rio, com signific&#226;ncia estat&#237;stica lim&#237;trofe, comparativamente aos que n&#227;o a receberam (p=0,06; RC=0,45; IC: 0,19-1,04). A suspens&#227;o dos betabloqueadores no p&#243;s-operat&#243;rio acarretou em aumento da incid&#234;ncia de fibrila&#231;&#227;o atrial no nosso estudo, mas sem diferen&#231;a estat&#237;stica (p=0,37; RC=0,48; IC: 0,10-2,07). De forma geral, a utiliza&#231;&#227;o de betabloqueadores em qualquer momento (pr&#233;, p&#243;s ou ambos os per&#237;odos) representou fator de prote&#231;&#227;o para o desenvolvimento de fibrila&#231;&#227;o atrial em rela&#231;&#227;o aos pacientes que n&#227;o o fizeram (p=0,01; RC=0,38; IC: 0,17-0,83).  </p>
    <p>Aumento de tempo de interna&#231;&#227;o hospitalar teve rela&#231;&#227;o direta com fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria, sendo que a m&#233;dia de perman&#234;ncia foi de 16,9 &#177; 12,3 dias para pacientes com fibrila&#231;&#227;o atrial <italic>vs</italic> 9,2 &#177; 4,0 dias para os sem fibrila&#231;&#227;o atrial (p&lt;0,001) (<xref ref-type="fig" rid="fig3">fig. 3</xref>).</p>
    <fig id="fig3">
      <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf03.jpg"/></fig>
    <p>Nove pacientes, 6 portadores de valvulopatia a&#243;rtica e 3 de cardiopatia isqu&#234;mica, apresentaram acidente vascular cerebral ou &#243;bito (desfecho combinado) no p&#243;s-operat&#243;rio, sendo que 7 tinham fibrila&#231;&#227;o atrial (p=0,02). Dos 45 pacientes que apresentaram fibrila&#231;&#227;o atrial, 11,1% desenvolveram acidente vascular cerebral e no grupo dos que n&#227;o a apresentaram houve 1,9% de acidente vascular cerebral (p=0,02) (<xref ref-type="fig" rid="fig4">fig.4</xref>). A fibrila&#231;&#227;o atrial n&#227;o se relacionou com tromboembolismo pulmonar (p=0,72) ou infarto agudo do mioc&#225;rdio perioperat&#243;rio (p=0,54).</p>
    <fig id="fig4">
      <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf04.jpg"/></fig>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Este estudo analisou 158 pacientes no per&#237;odo p&#243;s-operat&#243;rio de cirurgia card&#237;aca, procurando avaliar fatores de risco pr&#233;, trans e p&#243;s-operat&#243;rios relacionados &#224; fibrila&#231;&#227;o atrial, bem como a morbimortalidade associada com esta arritmia.  </p>
    <p>Na literatura, a incid&#234;ncia de fibrila&#231;&#227;o atrial varia de 17% a 33% em cirurgias de revasculariza&#231;&#227;o mioc&#225;rdica e de 38% a 64% em p&#243;s-operat&#243;rio de cirurgias valvares<sup>3</sup>. Para cirurgias card&#237;acas em geral, a incid&#234;ncia oscila de 20% a 40%<sup>11</sup>. Dados semelhantes aos de nosso estudo.  </p>
    <p>Segundo Maisel e cols.<sup>12</sup> o pico de incid&#234;ncia da fibrila&#231;&#227;o atrial ocorreu no 2&#186; e 3&#186; dias de p&#243;s-operat&#243;rio, de acordo com nossos dados, onde 63% dos pacientes a apresentaram nesse per&#237;odo.  </p>
    <p>Loubani e cols.<sup>13</sup> observaram que 50% dos pacientes que desenvolveram fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio de cirurgia card&#237;aca permaneceram com a arritmia no dia da alta hospitalar. Todos os 45 casos de fibrila&#231;&#227;o atrial da presente an&#225;lise receberam alta em ritmo sinusal, o que retrata o tipo de abordagem da nossa institui&#231;&#227;o, que prioriza a revers&#227;o ao ritmo sinusal.  </p>
    <p>O conhecimento dos fatores de risco para fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria parece revestir-se de fundamental import&#226;ncia para a elabora&#231;&#227;o de medidas de profilaxia e tratamento desta arritmia<sup>14-16</sup>. A idade &#233; o fator de risco mais citado na literatura<sup>1,3,9,17</sup>, provavelmente devido ao maior conte&#250;do de col&#225;geno atrial em pacientes idosos<sup>18</sup>. Outros fatores registrados na literatura s&#227;o doen&#231;a pulmonar obstrutiva cr&#244;nica<sup>7,10</sup>, doen&#231;a valvar mitral<sup>10,19</sup>, uso de inotr&#243;picos<sup>19</sup>, hist&#243;ria pr&#233;via de fibrila&#231;&#227;o atrial<sup>10</sup> e pericardite<sup>20</sup>. No presente estudo, a idade &gt; 70 anos mostrou-se fator de risco para fibrila&#231;&#227;o atrial.  </p>
    <p>A n&#227;o utiliza&#231;&#227;o de betabloqueadores durante o per&#237;odo de interna&#231;&#227;o tamb&#233;m associou-se fortemente &#224; fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria no nosso estudo. Na literatura, a interrup&#231;&#227;o dos betabloqueadores &#233; um fator muito importante no desencadeamento da arritmia p&#243;s-operat&#243;ria<sup>21</sup>. Na nossa an&#225;lise, a compara&#231;&#227;o da interrup&#231;&#227;o dos betabloqueadores com sua manuten&#231;&#227;o no p&#243;s-operat&#243;rio demonstrou diminui&#231;&#227;o da incid&#234;ncia de fibrila&#231;&#227;o atrial, apesar de n&#227;o ter havido diferen&#231;a significativa, provavelmente pelo pequeno n&#250;mero de pacientes da amostra. Na an&#225;lise multivariada, o uso de betabloqueadores no pr&#233;-operat&#243;rio mostrou-se fator de prote&#231;&#227;o para a fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria.  </p>
    <p>Quanto &#224; etiologia da doen&#231;a cir&#250;rgica, a cirurgia valvar a&#243;rtica mostrou ser um fator associado com grande incid&#234;ncia de fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria, atingindo valor semelhante ao da etiologia mitral. Fatores associados &#224; troca valvar a&#243;rtica que podem explicar esse resultado s&#227;o idade avan&#231;ada, crescimento atrial esquerdo, administra&#231;&#227;o de agentes inotr&#243;picos, assist&#234;ncia ventilat&#243;ria prolongada, acidose p&#243;s-operat&#243;ria, desequil&#237;brio eletrol&#237;tico e desordens da condu&#231;&#227;o atrioventricular e intraventricular<sup>22</sup>.  </p>
    <p>Outro importante fator &#233; a hipocalemia no per&#237;odo pr&#233;-operat&#243;rio. Wahr e cols.<sup>23</sup> observaram que valores de pot&#225;ssio &lt;3,5mmol/l estavam associados a maior incid&#234;ncia de arritmias. No presente estudo, hipocalemia n&#227;o correlacionou-se &#224; fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio (p=0,07).  </p>
    <p>No nosso trabalho um fator de risco p&#243;s-operat&#243;rio bastante significativo avaliado por regress&#227;o log&#237;stica, foi o balan&#231;o h&#237;drico total excessivo nas primeiras 24 horas. Observamos que os pacientes que desenvolveram fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria tiveram um balan&#231;o h&#237;drico maior do que os que n&#227;o a desenvolveram. Notamos ainda que houve 1% de risco adicional para fibrila&#231;&#227;o atrial para cada mililitro acumulado acima da m&#233;dia do balan&#231;o h&#237;drico. Neste caso a arritmia pode ter sido desencadeada pela distens&#227;o atrial<sup>24</sup>.  </p>
    <p>O tempo de isquemia e o de circula&#231;&#227;o extracorp&#243;rea n&#227;o apresentaram diferen&#231;a significativa entre os pacientes que desenvolveram fibrila&#231;&#227;o atrial e aqueles que se mantiveram em ritmo sinusal. Dados que confirmam estudos anteriores<sup>3,25,26</sup> onde &#233; comparada a incid&#234;ncia de fibrila&#231;&#227;o atrial em pacientes que se submeteram &#224; cirurgia card&#237;aca convencional e &#224; cirurgia sem circula&#231;&#227;o extracorp&#243;rea, n&#227;o podendo salientar o papel da circula&#231;&#227;o extracorp&#243;rea como sendo um fator predisponente.  </p>
    <p>O aumento atrial esquerdo tamb&#233;m &#233; apontado na literatura como um fator associado &#224; fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria<sup>10</sup>. Em uma pesquisa<sup>27</sup>, utilizando ecocardiografia transesof&#225;gica, o aumento do &#225;trio esquerdo n&#227;o foi preditor desta arritmia. Na nossa s&#233;rie, o aumento do &#225;trio esquerdo avaliado pela ecocardiografia transtor&#225;cica no per&#237;odo pr&#233;-operat&#243;rio, n&#227;o evidenciou correla&#231;&#227;o com fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio. A an&#225;lise da onda P por eletrocardiografia convencional de 12 deriva&#231;&#245;es tamb&#233;m n&#227;o apontou associa&#231;&#227;o significativa entre fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria e crescimento de &#225;trio esquerdo<sup>28</sup>.  </p>
    <p>Neste estudo, a insufici&#234;ncia card&#237;aca esquerda no pr&#233;-operat&#243;rio mostrou-se associada &#224; fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio, confirmando dados anteriores de Mayr e cols.<sup>5</sup>. Um fator que se mostrou relacionado, em an&#225;lise multivariada, com fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria foi o tempo de cirurgia excessivo. Esse fator, associado a outros fatores significativos, em an&#225;lises bivariadas relacionados com fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria, como tempo de perman&#234;ncia de drenos, agita&#231;&#227;o psicomotora, insufici&#234;ncia respirat&#243;ria e congest&#227;o pulmonar no p&#243;s-operat&#243;rio, pode significar que o paciente que desenvolve fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio &#233; aquele com maior comprometimento sist&#234;mico. Assim, a fibrila&#231;&#227;o atrial poderia ser considerada um marcador de gravidade no p&#243;s-operat&#243;rio de cirurgia card&#237;aca.  </p>
    <p>Encontramos uma associa&#231;&#227;o significativa entre fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria e maior incid&#234;ncia de acidente vascular cerebral. Creswell e cols.<sup>29</sup> relataram que pacientes desenvolvendo fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria tinham 3,3% de incid&#234;ncia de acidente vascular cerebral, enquanto naqueles que n&#227;o a desenvolveram, a incid&#234;ncia foi de apenas 1,4%, (p&lt;0,005). O nosso estudo revelou uma incid&#234;ncia superior &#224; da literatura, de acidente vascular cerebral em pacientes que apresentaram fibrila&#231;&#227;o atrial. Uma pesquisa analisando fatores de risco para a ocorr&#234;ncia de acidente vascular cerebral e ataque isqu&#234;mico transit&#243;rio em p&#243;s-operat&#243;rio de cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica constatou que fibrila&#231;&#227;o atrial e baixo d&#233;bito card&#237;aco estavam significativamente relacionados com aquelas complica&#231;&#245;es<sup>30</sup>.  </p>
    <p>Kim e cols.<sup>31</sup>, comparando tempo de interna&#231;&#227;o hospitalar e custos em pacientes com e sem fibrila&#231;&#227;o atrial p&#243;s-cirurgia card&#237;aca, revelaram que o impacto dessa arritmia sobre o per&#237;odo de hospitaliza&#231;&#227;o n&#227;o foi muito importante. No entanto, um estudo observacional com 3.855 pacientes submetidos &#224; cirurgia card&#237;aca verificou diferen&#231;as significativas na m&#233;dia de interna&#231;&#227;o hospitalar em pacientes com e sem fibrila&#231;&#227;o atrial<sup>19</sup>. No nosso estudo, o tempo de interna&#231;&#227;o hospitalar foi quase duas vezes maior nos pacientes com fibrila&#231;&#227;o atrial do que nos que se mantiveram em ritmo sinusal. A an&#225;lise multivariada mostrou uma rela&#231;&#227;o direta entre fibrila&#231;&#227;o atrial e aumento do tempo de interna&#231;&#227;o hospitalar.  </p>
    <p>Os nossos dados est&#227;o de acordo com as recomenda&#231;&#245;es anteriores de utiliza&#231;&#227;o de betabloqueadores no pr&#233;-operat&#243;rio de cirurgia card&#237;aca, se n&#227;o houver contra-indica&#231;&#245;es, e a sua manuten&#231;&#227;o no p&#243;s-operat&#243;rio, principalmente em pacientes &gt; 70 anos e nos valvopatas mitro-a&#243;rticos, sugerindo que um rigoroso balan&#231;o h&#237;drico seja necess&#225;rio para diminuir a incid&#234;ncia dessa arritmia no per&#237;odo p&#243;s-operat&#243;rio.  </p>
    <p>A maior limita&#231;&#227;o deste estudo, semelhante &#224; de outras publica&#231;&#245;es, foi n&#227;o ter sido feita monitoriza&#231;&#227;o com telemetria durante o per&#237;odo de recupera&#231;&#227;o dos pacientes, o que pode ter subestimado a real incid&#234;ncia de fibrila&#231;&#227;o atrial. No entanto, durante o per&#237;odo de perman&#234;ncia na UTI, de maior suscetibilidade para arritmias, a maioria dos pacientes esteve monitorizada e sob vigil&#226;ncia permanente da equipe de enfermagem. Al&#233;m disso, os epis&#243;dios de arritmia considerados foram os de relev&#226;ncia cl&#237;nica. Como a incid&#234;ncia de fibrila&#231;&#227;o atrial encontrada vai ao encontro do destacado pela literatura, &#233; prov&#225;vel que esta limita&#231;&#227;o n&#227;o tenha sido de grande magnitude.  </p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Em conclus&#227;o, a incid&#234;ncia de fibrila&#231;&#227;o atrial em p&#243;s-operat&#243;rio de cirurgia card&#237;aca foi de 28,5%. Fatores de risco pr&#233;-operat&#243;rios associados com maior incid&#234;ncia de fibrila&#231;&#227;o atrial foram idade &gt; 70 anos, aus&#234;ncia de betabloqueadores e doen&#231;a valvar a&#243;rtica. Fatores p&#243;s-operat&#243;rios foram agita&#231;&#227;o psicomotora,tempo de perman&#234;ncia dos drenos, insufici&#234;ncia respirat&#243;ria e congest&#227;o pulmonar. Quatro fatores tiveram associa&#231;&#227;o independente com desenvolvimento de fibrila&#231;&#227;o atrial no p&#243;s-operat&#243;rio na an&#225;lise multivariada: insufici&#234;ncia card&#237;aca esquerda no pr&#233;-operat&#243;rio, balan&#231;o h&#237;drico total e tempo de cirurgia excessivos, al&#233;m do uso de betabloqueadores, que se constituiu em um fator de prote&#231;&#227;o contra fibrila&#231;&#227;o atrial p&#243;s-operat&#243;ria. Fibrila&#231;&#227;o atrial foi associada com aumento do tempo de interna&#231;&#227;o hospitalar e com maior incid&#234;ncia de acidente vascular cerebral ou &#243;bito no p&#243;s-operat&#243;rio (desfecho combinado).  </p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Endere&#231;o para correspond&#234;ncia</bold>
        </label>
        <p> Av. Princesa Isabel, 370 </p>
        <p> Unid. Pesquisa &#150; Porto Alegre &#150; RS </p>
        <p> Cep 90620-001 </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="gglima.pesquisa@cardiologia.org.br">gglima.pesquisa@cardiologia.org.br</email>
        </p>
      </fn>
    </p>
    <p>Recebido para Publica&#231;&#227;o em 11/7/03 </p>
    <p> Aceito em 6/1/04  </p>
  </body>
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              <surname>Rosenbloom</surname>
              <given-names>M</given-names>
            </name>
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        <mixed-citation>30. Engelman DT,    Cohn LrrH, Rizzo RJ. Incidence and predictors of TIAS and stroke following coronary    artery bypass surgery: report and collective review. Heart Surg Forum 1999;    2: 242-5.  </mixed-citation>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Risk factors, morbidity, and mortality associated with atrial fibrillation in the postoperative period of cardiac surgery</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>OBJECTIVE: To determine the incidence of atrial fibrillation in the postoperative period of cardiac surgery, its impact on morbidity, mortality, and hospital stay, and to analyze the risk factors in the pre, trans, and postoperative periods. METHOD: Contemporary cohort study with 158 adult patients undergoing cardiac surgery, of whom those with atrial fibrillation in the preoperative period were excluded. The patients were assessed with continuous cardiac monitoring and daily electrocardiograms. Any episode of irregular rhythm with the presence of f waves of variable morphology and amplitude was considered atrial fibrillation. RESULTS: The general incidence of atrial fibrillation was 28.5%, being 21.6% for revascularized patients and 44.3% for those undergoing valvular repair. Factors independently associated with atrial fibrillation were left heart failure in the preoperative period (p=0.05; RC=2.2), total fluid balance (p=0.01; RC=1.0), duration of surgery (p=0.03; RC=1.01) [and other associated factors, age &gt; 70 years, aortic valvular disease, psychomotor agitation, length of installation of the drains, pulmonary congestion and respiratory insufficiency in the postoperative period]. The use of beta-blockers (p=0.01; RC=0.3) was a protective factor. Atrial fibrillation in the postoperative period was associated with an increase in the length of hospital stay (16.9&#177;12.3 days versus 9.2&#177;4.0 days, p&lt;0.001) and a greater incidence of stroke or postoperative death (p=0.02). CONCLUSION: The incidence of atrial fibrillation in the postoperative period of cardiac surgery was high and caused a significant increase in morbidity, mortality, and the length of hospital stay. Among the independent risk factors, excessive fluid balance is significant. The use of beta-blockers was identified as a protective factor.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>atrial fibrillation</kwd>
        <kwd>arrhythmias</kwd>
        <kwd>cardiac surgery</kwd>
        <kwd>postoperative care</kwd>
        <kwd>risk factors</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>Risk factors, morbidity, and mortality associated with atrial fibrillation in the postoperative period of cardiac surgery </p>
      <p>Rog&#233;rio Gomes da Silva; Gustavo Glotz de Lima; Andr&#233;ia Laranjeira; Altamiro Reis da Costa; Edemar Pereira; Rubem Rodrigues</p>
      <p> Porto Alegre, RS - Brazil</p>
      <p>Instituto de Cardiologia do Rio Grande do Sul/Funda&#231;&#227;o Universit&#225;ria de Cardiologia </p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Correspondence</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>OBJECTIVE: </bold>To determine the incidence of atrial fibrillation in the postoperative period of cardiac surgery, its impact on morbidity, mortality, and hospital stay, and to analyze the risk factors in the pre, trans, and postoperative periods.</p>
      <p><bold>METHOD: </bold>Contemporary cohort study with 158 adult patients undergoing cardiac surgery, of whom those with atrial fibrillation in the preoperative period were excluded. The patients were assessed with continuous cardiac monitoring and daily electrocardiograms. Any episode of irregular rhythm with the presence of f waves of variable morphology and amplitude was considered atrial fibrillation.</p>
      <p><bold>RESULTS: </bold>The general incidence of atrial fibrillation was 28.5%, being 21.6% for revascularized patients and 44.3% for those undergoing valvular repair. Factors independently associated with atrial fibrillation were left heart failure in the preoperative period (p=0.05; RC=2.2), total fluid balance (p=0.01; RC=1.0), duration of surgery (p=0.03; RC=1.01) [and other associated factors, age &gt; 70 years, aortic valvular disease, psychomotor agitation, length of installation of the drains, pulmonary congestion and respiratory insufficiency in the postoperative period]. The use of beta-blockers (p=0.01; RC=0.3) was a protective factor. Atrial fibrillation in the postoperative period was associated with an increase in the length of hospital stay (16.9&#177;12.3 days versus 9.2&#177;4.0 days, p&lt;0.001) and a greater incidence of stroke or postoperative death (p=0.02).</p>
      <p><bold>CONCLUSION: </bold>The incidence of atrial fibrillation in the postoperative period of cardiac surgery was high and caused a significant increase in morbidity, mortality, and the length of hospital stay. Among the independent risk factors, excessive fluid balance is significant. The use of beta-blockers was identified as a protective factor.</p>
      <p><bold>Key words:</bold> atrial fibrillation, arrhythmias, cardiac surgery, postoperative care, risk factors</p>
      <p>Atrial arrhythmias are common in the postoperative period of cardiothoracic surgery. They may occur in 11% to 40% of patients after myocardial revascularization surgery and in approximately 50% of those undergoing valvular surgery<sup>1,2</sup>. Atrial fibrillation is the most frequent arrhythmia after cardiac surgery<sup>3</sup>. It is commonly an auto-limited condition, which rarely causes perioperative death, but can extend the length of hospital stay, increasing costs. Sometimes, it may be considered a cause of perioperative acute myocardial infarction and thromboembolic phenomena<sup>3,4</sup>. The following risk factors are associated with atrial fibrillation in the postoperative period of cardiac surgery: left heart failure, systemic inflammatory response syndrome, septicemia or multisystem organ failure<sup>5</sup>, suspension of beta-blockers<sup>6</sup>, chronic obstructive pulmonary disease<sup>7</sup>, and the need for mechanical ventilatory support<sup>8</sup>. Advanced age, however, is the risk factor most frequently associated with postoperative atrial fibrillation<sup>9</sup>. In patients at higher risk, preventive measures should be considered<sup>10</sup>. </p>
      <p>This prospective and observational study aimed at assessing the incidence of atrial fibrillation in the postoperative period of cardiac surgery and the pre, trans, and postoperative risk factors associated with that arrhythmia in a national cardiology referral center, and at analyzing morbidity, mortality, and the length of hospital stay related to that arrhythmia. </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>From January to May 2002, 158 patients undergoing cardiac surgery in a referral institution were selected in the immediate postoperative phase. </p>
      <p>The sample comprised patients undergoing cardiac surgery on a systematically selected day, which differed consecutively from week to week, such that if carried out on Monday on a given week, it would be carried out on Tuesday the following week, and so forth. All patients selected during the study were followed up until the discharge day, and no patient or protocol information was lost during follow-up. The mean number of patients selected per month was 31.8. </p>
      <p>This is a contemporary cohort study, in which the patients were assessed at 4 distinct times: in the immediate postoperative period; in the intensive care unit (postoperative ICU); on discharge from the postoperative ICU; and on hospital discharge. </p>
      <p>This study comprised patients undergoing cardiac surgery, with or without extracorporeal circulation, due to ischemic or valvular heart disease. Those with a history of preoperative atrial fibrillation were excluded. </p>
      <p>In each of the 4 phases of assessment, a protocol previously approved by the Committee of Ethics on Research with data to be investigated and written informed consent was used. In the selection phase, the demographic and preoperative data were collected. </p>
      <p>All patients were examined personally by the author, who also analyzed the pre and postoperative examinations. In the postoperative ICU stay phase and in the discharge from the ICU phase, the patients were assessed daily from the clinical and laboratory points of view. </p>
      <p>Cardiac rhythm was assessed through continuous cardiac monitoring in all patients during a minimum period of 72 hours (postoperative ICU stay phase) and through daily electrocardiographic examinations until hospital discharge. Additional electrocardiographies were performed when patients reported palpitations, tachycardia, or angina, and postoperative biochemical, hematological, and radiological examinations were performed according to the routine of the postoperative service at our institution. </p>
      <p>Any episode of supraventricular arrhythmia, whose electrocardiographic tracing had f waves of variable morphology and amplitude with irregular ventricular rhythm, was considered atrial fibrillation (primary outcome). </p>
      <p>Episodes of atrial fibrillation that had a minimum duration of 15 minutes or required treatment due to symptoms or hemodynamic instability were included in the study. The use of a vasopressor, when administered at a dosage greater than 5&#181;g/kg/min longer than the first 2 hours of the postoperative period, was considered. </p>
      <p>Postoperative anemia was defined as a hematocrit lower than 30% or hemoglobin below 10 mg/dL, or both, or in case of transfusion of at least 1 unit of red blood cell concentrate and hypokalemia, as a serum potassium level below 3.5 mmol/L. </p>
      <p>Initially, frequency tables for all variables contained in the database were generated. Then, the mean &#177; standard deviation for quantitative variables and the percentage for qualitative variables were calculated. The strength of the association of each factor for postoperative atrial fibrillation was measured through the estimates of the relative risk with 95% confidence intervals. The significance of these associations was determined by the chi-square test, and, when necessary, by the Fischer exact test. Comparisons of quantitative data between the groups were performed by using the Student <italic>t</italic> test for independent samples. </p>
      <p>A mathematical model based on multivariate logistic regression was used for establishing the best model for predicting and controlling the potential effect of confusion between the factors analyzed and the occurrence of postoperative atrial fibrillation. Variables reported as relevant in the literature and those showing a strong association with the outcome in the bivariate analysis performed were selected to be included in the logistic model. The significance level adopted was 0.05. The analysis of data was performed by using the SPSS software program, version 8.0. </p>
      <p>
        <bold>Results</bold>
      </p>
      <p>In our sample, males (64%) and coronary artery disease (70%) predominated. In regard to the patients, 61% were hypertensive, 60% smokers, 58% had unstable angina, and 54% used beta-blockers. The mean age of the patients was 60.9&#177;11.2 years. </p>
      <p>The general incidence of postoperative atrial fibrillation was 28.5% (45 cases). Of the 158 patients followed up, the mean number of atrial fibrillation per month was 9 cases. </p>
      <p><xref ref-type="table" rid="tab1-body2">Table I</xref> shows the preoperative categorical variables, the demographic characteristics of the patients, which underwent bivariate analysis in regard to the occurrence of atrial fibrillation. The following 4 risk factors significantly related to the greater incidence of postoperative atrial fibrillation were identified: aortic valvular disease (p=0.02); preoperative left heart failure (p=0.006); no previous use of beta-blockers (p=0.02); and age &gt; 70 years (p=0.03). Of the 20 cases with mitral valvular disease, 9 had atrial fibrillation (45%; p=0.07). Previous acute myocardial infarction, enlargement of the P wave on electrocardiography, emergency surgery, reoperation, and unstable angina were not related to postoperative atrial fibrillation. Coronary artery disease showed an inverse relation with postoperative atrial fibrillation.</p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt01-en.jpg"/></table-wrap>
      <p>Comparing patients undergoing myocardial revascularization with those undergoing valvular heart surgeries, a greater incidence of postoperative atrial fibrillation was found among the latter (p=0.008; RR=2.18; CI: 1.28-3.70). </p>
      <p>The bivariate analysis for postoperative categorical variables (<xref ref-type="table" rid="tab2-body2">tab. II</xref>) identified 3 factors associated with atrial fibrillation. The most significant factor was psychomotor agitation (p=0.008), in which atrial fibrillation occurred in 9 out of 15 patients. Respiratory insufficiency and pulmonary congestion were also significant findings in our study. Pericardial friction, perioperative acute myocardial infarction, and use of dopamine were factors not related to postoperative atrial fibrillation.</p>
      <table-wrap id="tab2-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt02-en.jpg"/></table-wrap>
      <p>In regard to the continuous variables associated with postoperative atrial fibrillation, the bivariate analysis showed that the increased length of installation of the drains is a significant factor (p=0.04). Patients with a greater incidence of atrial fibrillation showed crystalloid, colloid, and total fluid balances significantly more positive than those who did not have that arrhythmia (p=0.03, 0.04, and 0.04, respectively). The durations of extracorporeal circulation and ischemia were not significant in the present study. The preoperative potassium level determined no difference (p=0.07). The other postoperative biochemical and hematological measurements were not statistically significant (serum levels of potassium, creatinine, and sodium; glycemia; hematocrit; and hemoglobin) (<xref ref-type="table" rid="tab3-body2">tab. III</xref>).</p>
      <table-wrap id="tab3-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt03-en.jpg"/></table-wrap>
      <p>Multivariate logistic regression identified 4 statistically independent predictors of postoperative atrial fibrillation. Left heart failure was identified as a preoperative variable, whilst an exceedingly long time of surgery was recognized as a significantly independent transoperative variable. In regard to the postoperative variables, respiratory insufficiency with a borderline statistical significance (p=0.07) showed a clinically important association with a greater incidence of atrial fibrillation. The excessively positive total fluid balance was a significant risk factor for triggering that arrhythmia (1% of additional risk for each milliliter accumulated above the mean fluid balance). The use of beta-blockers was a protective factor for the development of postoperative atrial fibrillation. Respiratory insufficiency (p=0.07) showed no clinically important association with a greater incidence of that arrhythmia (<xref ref-type="table" rid="tab4-body2">tab. IV</xref>).</p>
      <table-wrap id="tab4-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gt04-en.jpg"/></table-wrap>
      <p><xref ref-type="fig" rid="fig1-body2">Figure 1</xref> depicts the postoperative incidence of atrial fibrillation as fallows: most patients (63%) had arrhythmia on the second (13 cases) and third (16 cases) postoperative days; 11% of the patients had atrial fibrillation on the forth postoperative day; and 8% had that arrhythmia on the fifth postoperative day. Atrial fibrillation in the postoperative period of cardiac surgery 8% had that arrhythmia on the fifth postoperative day. Atrial fibrillation was observed in 39 (86.7%) patients during their stay in the intensive care unit (ICU), and 79% had the arrhythmia up to the third day in the ICU.</p>
      <fig id="fig1-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf01-en.jpg"/></fig>
      <p>All 45 patients with postoperative atrial fibrillation were discharged with sinus rhythm. Of the others, 18 (40%) spontaneously reverted to sinus rhythm before any therapeutic measures were taken. Most patients analyzed in this study were treated and the arrhythmia was reverted with the intravenous administration of amiodarone (40%). Eight patients with spontaneous reversion received intravenous digitalis for controlling ventricular response. Nine patients underwent electrical cardioversion as follows: 4 due to hemodynamic instability and the other 5 treated with amiodarone prior to electric cardioversion. </p>
      <p>Of the patients receiving beta-blockers, those receiving the medication in the pre and postoperative periods had a lower incidence of atrial fibrillation (12.5%). Sixty-one patients with a 23% incidence of atrial fibrillation discontinued the use of beta-blockers in the postoperative period. Patients who did not receive beta-blockers in the pre- and postoperative periods had a greater incidence of atrial fibrillation (39.7%; p=0.017) (<xref ref-type="fig" rid="fig2-body2">fig. 2</xref>).</p>
      <fig id="fig2-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf02-en.jpg"/></fig>
      <p>The use of beta-blockers in the pre and postoperative periods (p=0.028; RC=0.22; CI: 0.05-0.88) provided protection against atrial fibrillation as compared with those who did not use the drug. Prevention of atrial fibrillation was also observed in patients who received the drug only in the preoperative period, with a borderline statistical significance, as compared with those who did not receive it (p=0.06; RC=0.45; CI: 0.19-1.04). Suspension of the beta-blockers in the postoperative period caused an increase in the incidence of atrial fibrillation in our study, but with no statistical difference (p=0.37; RC=0.48; CI: 0.10-2.07). Usually, the use of beta-blockers at any moment (pre or postoperative periods, or both periods) represented a protective factor against the development of atrial fibrillation as compared with the nonuse of them (p=0.01; RC=0.38; CI: 0.17-0.83). </p>
      <p>The increase in the length of hospital stay had a direct relation with postoperative atrial fibrillation, the mean stay being 16.9 &#177; 12.3 days for patients with atrial fibrillation versus 9.2 &#177; 4.0 days for those with no atrial fibrillation (p &lt; 0.001) (<xref ref-type="fig" rid="fig3-body2">fig.3</xref>).</p>
      <fig id="fig3-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf03-en.jpg"/></fig>
      <p>Nine patients, 6 with aortic valvular disease and 3 with ischemic heart disease, had stroke or died (combined outcome) in the postoperative period, 7 of whom had atrial fibrillation (p=0.02). Of the 45 patients with atrial fibrillation, 11.1% developed stroke, and among those with no atrial fibrillation, only 1.9% had stroke (p=0.02) (<xref ref-type="fig" rid="fig4-body2">fig. 4</xref>). Atrial fibrillation was related to neither pulmonary thromboembolism (p=0.72) nor perioperative acute myocardial infarction (p=0.54).</p>
      <fig id="fig4-body2">
        <graphic xlink:href="1678-4170-abc-83-02-0099-00002-gf04-en.jpg"/></fig>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>This study comprised 158 patients in the postoperative period of cardiac surgery, and aimed at assessing the pre, trans, and postoperative risk factors related to atrial fibrillation, and also the morbidity and mortality associated with that arrhythmia. </p>
      <p>In the literature, the incidence of atrial fibrillation ranges from 17% to 33% in myocardial revascularization surgeries, and from 38% to 64% in the postoperative period of valvular heart surgeries <sup>3</sup>. For cardiac surgeries in general, the incidence ranges from 20% to 40% <sup>11</sup>. These values are similar to those of our study. </p>
      <p>According to Maisel et al <sup>12</sup>, the peak incidence of atrial fibrillation occurred on the second and third postoperative days. This is in accordance with our data, in which 63% of the patients had that arrhythmia in the same period. </p>
      <p>Loubani et al <sup>13</sup> reported that 50% of the patients who developed atrial fibrillation in the postoperative period of cardiac surgery remained with the arrhythmia on the day of hospital discharge. All 45 patients with atrial fibrillation in our study were discharged from the hospital with sinus rhythm, indicating that the approach in our institution prioritizes reversion to sinus rhythm. </p>
      <p>Knowledge about the risk factors for postoperative atrial fibrillation seems to have a fundamental importance in the elaboration of prophylactic and therapeutical measures for that arrhythmia <sup>14-16</sup>. Age is the most cited risk factor in the literature <sup>1,3,9,17</sup>, probably due to the higher content of atrial collagen in elderly patients <sup>18</sup>. Other factors reported in the literature include chronic obstructive pulmonary disease <sup>7,10</sup>, mitral valvular disease <sup>10,19</sup>, use of inotropic agents <sup>19</sup>, previous history of atrial fibrillation <sup>10</sup>, and pericarditis <sup>20</sup>. In the present study, age &gt; 70 years proved to be a risk factor for atrial fibrillation. </p>
      <p>The nonuse of beta-blockers during hospital stay was also strongly associated with postoperative atrial fibrillation in our study. In the literature, the suspension of beta-blockers is a very important factor for triggering postoperative arrhythmia <sup>21</sup>. In our study, the comparison of the suspension of beta-blockers with their maintenance in the postoperative period caused a decrease in the incidence of atrial fibrillation, although no significant difference occurred, probably due to the small number of patients in the sample. In the multivariate analysis, the use of beta-blockers in the preoperative period proved to be a protective factor of postoperative atrial fibrillation. </p>
      <p>In regard to the etiology of the surgical disease, aortic valvular disease proved to be a factor associated with a great incidence of postoperative atrial fibrillation, reaching a value similar to that of mitral etiology. Factors associated with aortic valvular replacement that may explain this result are as follows: advanced age, left atrial enlargement, administration of inotropic agents, prolonged ventilatory support, postoperative acidosis, electrolyte imbalance, and disorders in atrioventricular and intraventricular conduction <sup>22</sup>. </p>
      <p>Another important factor is preoperative hypokalemia. Wahr et al <sup>23</sup> reported that potassium levels &lt; 3.5 mmol/L were associated with a greater incidence of arrhythmias. In our study, hypokalemia showed no correlation with postoperative atrial fibrillation (p=0.07). </p>
      <p>In our study, a very significant postoperative risk factor assessed through logistic regression was an excessive total fluid balance in the first 24 hours. The patients who developed postoperative atrial fibrillation had a greater fluid balance than those who did not develop it. A 1% additional risk of atrial fibrillation was observed for each milliliter accumulated above the mean fluid balance. In this case, arrhythmia may have been triggered by atrial distension <sup>24</sup>. </p>
      <p>The durations of ischemia and extracorporeal circulation showed no significant differences in the patients who developed atrial fibrillation and those who maintained sinus rhythm. These data confirm that of previous studies <sup>3,25,26</sup>, which compared the incidence of atrial fibrillation in patients who underwent conventional cardiac surgery and surgery without extracorporeal circulation, and could not emphasize the role played by extracorporeal circulation as a predisposing factor. </p>
      <p>Left atrial enlargement has also been reported as a factor associated with postoperative atrial fibrillation<sup> 10</sup>. In a study <sup>27</sup> using transesophageal echocardiography, left atrial enlargement did not predict that arrhythmia. In our case series, left atrial enlargement assessed through transthoracic echocardiography in the preoperative period showed no correlation with postoperative atrial fibrillation. The analysis of the P wave by use of 12-lead conventional electrocardiography showed no significant association between postoperative atrial fibrillation and left atrial enlargement <sup>28</sup>. </p>
      <p>In this study, preoperative left heart failure proved to be associated with postoperative atrial fibrillation, confirming the previous results reported by Mayr et al <sup>5</sup> . In multivariate analysis, the excessive duration of surgery was a factor that proved to be related to postoperative atrial fibrillation. This factor in combination with other significant factors related to postoperative atrial fibrillation in bivariate analysis, such as length of installation of the drains, psychomotor agitation, respiratory insufficiency, and pulmonary congestion in the postoperative period, may indicate that the patient who develops postoperative atrial fibrillation is the one with the greatest systemic impairment. Therefore, atrial fibrillation can be considered a marker of severity in the postoperative period of cardiac surgery. </p>
      <p>We found a significant association between postoperative atrial fibrillation and a greater incidence of stroke. Creswell et al <sup>29</sup> reported that patients with postoperative atrial fibrillation had a 3.3% incidence of stroke, while those who did not develop it had an incidence of only 1.4% (p &lt; 0.005). Our study showed an incidence of stroke in patients with atrial fibrillation greater than that reported in the literature. A study <sup>30 </sup>assessing the risk factors for the occurrence of stroke and transient ischemic attack in the postoperative period of myocardial revascularization surgery reported that atrial fibrillation and low cardiac output were significantly related to those complications. </p>
      <p>Kim et al <sup>31</sup>, comparing the length of hospital stay and costs in patients with and without atrial fibrillation after cardiac surgery, reported that the impact of that arrhythmia on the length of hospital stay was not very important. However, an observational study<sup>19 </sup>with 3,855 patients undergoing cardiac surgery reported significant differences in the mean length of hospital stay for patients with and without atrial fibrillation. In our study, the length of hospital stay in patients with atrial fibrillation was almost two times greater than that in patients who sustained sinus rhythm. Multivariate analysis showed a direct relation between atrial fibrillation and the increase in the length of hospital stay. </p>
      <p>Our data are in accordance with previous recommendations for the use of beta-blockers in the preoperative period of cardiac surgery, provided no contraindications exist, and their maintenance in the postoperative period, mainly in patients &gt; 70 years and those with mitral-aortic valve diseases. Our data also suggest that a strict fluid balance is necessary to decrease the incidence of that arrhythmia in the postoperative period. </p>
      <p>The major limitation of this study, similarly to that reported in other publications, was the lack of telemetry monitoring during the patients' recovery period, which may have underestimated the actual incidence of atrial fibrillation. However, during the stay in the ICU, when patients are more susceptible to arrhythmias, most patients were monitored and under permanent surveillance of the nurse team. In addition, only the clinically relevant episodes of arrhythmia were considered. As the incidence of atrial fibrillation found in our study is in accordance with that reported in the literature, this limitation may not have been of great magnitude. </p>
      <p>In conclusion, the general incidence of atrial fibrillation in the postoperative period of cardiac surgery was 28.5%. Preoperative risk factors associated with a greater incidence of atrial fibrillation were as follows: age &gt; 70 years, aortic valvular disease, and nonuse of beta-blockers. Postoperative risk factors associated with a greater incidence of atrial fibrillation were as follows: psychomotor agitation, length of installation of the drains, respiratory insufficiency, and pulmonary congestion. In multivariate analysis, the following 4 factors had an independent association with the development of postoperative atrial fibrillation: preoperative left heart failure, total fluid balance, and excessive duration of surgery, in addition to the use of beta-blockers, which was a protective factor against postoperative atrial fibrillation. Atrial fibrillation was associated with an increase in the length of hospital stay and with a greater incidence of stroke or death in the postoperative period (combined outcome). </p>
      <p>
        <bold>References</bold>
      </p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <p>Correspondence to</p>
          <p> Rog&#233;rio Gomes da Silva</p>
          <p> IC/FUC &#150; Unidade de Pesquisa</p>
          <p> Av. Princesa Isabel, 370</p>
          <p> Cep 90620-001</p>
          <p> Porto Alegre, RS, Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="gglima.pesquisa@cardiologia.org.br">gglima.pesquisa@cardiologia.org.br</email>
          </p>
        </fn>
      </p>
      <p>Received: 7/11/03</p>
      <p> Accepted: 1/6/04 </p>
      <p>English version by Stela Maris Costalonga </p>
      <p><bold>Citalor<sup>&#174;</sup></bold> (atorvastatina c&#225;lcica) &#233; um agente hipolipemiante que diminui os n&#237;veis plasm&#225;ticos de colesterol e lipoprote&#237;nas atrav&#233;s da inibi&#231;&#227;o da HMG-CoA redutase e da s&#237;ntese de colesterol no f&#237;gado, ampliando o n&#250;mero de receptores de LDL hep&#225;ticos na superf&#237;cie da c&#233;lula, o que aumenta a absor&#231;&#227;o e o catabolismo do LDL. <bold>Indica&#231;&#245;es:</bold> para a redu&#231;&#227;o de n&#237;veis elevados de colesterol total, LDL-colesterol, apolipoprote&#237;na B e triglic&#233;rides em pacientes com hipercolesterolemia prim&#225;ria e hiperlipidemia combinada (mista); para o tratamento de pacientes com n&#237;veis elevados de triglic&#233;rides s&#233;ricos e de pacientes com disbetalipoproteinemia que n&#227;o respondem de forma adequada &#224; dieta; tamb&#233;m &#233; indicado para a redu&#231;&#227;o do colesterol total e do LDL-colesterol em pacientes com hipercolesterolemia familiar homozig&#243;tica, quando a resposta &#224; dieta e outras medidas n&#227;o-farmacol&#243;gicas forem inadequadas; em paciente com doen&#231;a cardiovascular e/ou dislipidemia, est&#225; indicado na S&#237;ndrome Coron&#225;ria Aguda, para a preven&#231;&#227;o secund&#225;ria do risco combinado de morte, infarto do mioc&#225;rdio n&#227;o-fatal, parada card&#237;aca e re-hospitaliza&#231;&#227;o de paciente com angina do peito (estudo MIRACL &#150; <italic>Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering</italic>). <bold>Contra-indica&#231;&#245;es:</bold> hipersensibilidade a qualquer componente de sua f&#243;rmula; doen&#231;a hep&#225;tica ativa ou eleva&#231;&#245;es persistentes inesperadas das transaminases s&#233;ricas que excedam em 3 vezes o limite superior da normalidade; durante a gravidez ou a lacta&#231;&#227;o; mulheres em idade f&#233;rtil que n&#227;o estejam utilizando medidas contraceptivas eficazes. <bold>Advert&#234;ncias e precau&#231;&#245;es:</bold> os pacientes devem ser aconselhados a relatar imediatamente a ocorr&#234;ncia inexplic&#225;vel de dor muscular, altera&#231;&#245;es da sensibilidade ou fraqueza muscular, principalmente se forem acompanhadas de malestar ou febre. Testes de fun&#231;&#227;o hep&#225;tica devem ser realizados antes do in&#237;cio do tratamento e, periodicamente, durante o tratamento. Pacientes que desenvolverem quaisquer sinais ou sintomas sugestivos de danos hep&#225;ticos devem ser monitorados at&#233; que a anormalidade se resolva. Se um aumento de AST e ALT (TGO e TGP) maior que 3 vezes o limite superior da normalidade persistir, recomenda-se a redu&#231;&#227;o da dose ou a descontinua&#231;&#227;o do tratamento. Citalor<sup>&#174;</sup> deve ser utilizado com precau&#231;&#227;o por pacientes que consomem quantidades apreci&#225;veis de &#225;lcool e/ou apresentam hist&#243;ria de doen&#231;a hep&#225;tica. O tratamento deve ser descontinuado no caso de ocorr&#234;ncia de n&#237;veis consideravelmente elevados de CPK ou de diagn&#243;stico ou suspeita de miopatia. O tratamento deve ser interrompido temporariamente ou descontinuado em qualquer paciente com uma condi&#231;&#227;o s&#233;ria e aguda sugestiva de miopatia ou que apresente um fator de risco que o predisponha ao desenvolvimento de insufici&#234;ncia renal secund&#225;ria &#224; rabdomi&#243;lise. <bold>Intera&#231;&#245;es medicamentosas:</bold> anti&#225;cidos (com hidr&#243;xido de magn&#233;sio e de alum&#237;nio), colestipol, digoxina, eritromicina/claritromicina, contraceptivos orais e inibidores da protease. <bold>Rea&#231;&#245;es adversas:</bold> constipa&#231;&#227;o, flatul&#234;ncia, dispepsia, dor abdominal, cefal&#233;ia, n&#225;usea, mialgia, astenia, diarr&#233;ia e ins&#244;nia. <bold>Posologia:</bold> as doses podem variar de 10 a 80 mg, em dose &#250;nica di&#225;ria, que pode ser administrada a qualquer hora do dia, com ou sem alimentos. As doses inicial e de manuten&#231;&#227;o devem ser individualizadas de acordo com os n&#237;veis basais de LDL-colesterol, o objetivo do tratamento e a resposta do paciente. Ap&#243;s o in&#237;cio do tratamento e/ou durante o ajuste de dose de atorvastatina, os n&#237;veis lip&#237;dicos devem ser analisados dentro de 2 a 4 semanas e a dose deve ser ajustada adequadamente. <italic>Hipercolesterolemia prim&#225;ria e hiperlipidemia combinada (mista):</italic> a maioria dos pacientes &#233; controlada com 10 mg de atorvastatina em dose &#250;nica di&#225;ria. <italic>Hipercolesterolemia familiar homozig&#243;tica:</italic> a maioria dos pacientes respondeu a 80 mg de atorvastatina com uma redu&#231;&#227;o maior que 15% no LDL-colesterol (18%-45%). A experi&#234;ncia no tratamento de pacientes pedi&#225;tricos (com doses de atorvastatina de at&#233; 80 mg/dia) &#233; limitada. <bold>Superdosagem:</bold> o paciente deve receber tratamento sintom&#225;tico e, conforme a necessidade, devem ser institu&#237;das medidas de suporte. Devido &#224; alta liga&#231;&#227;o &#224;s prote&#237;nas plasm&#225;ticas, a hemodi&#225;lise n&#227;o deve aumentar a depura&#231;&#227;o da atorvastatina significantemente. <bold>Apresenta&#231;&#245;es:</bold> comprimidos revestidos de 10 mg, 20 mg, 40 mg e 80 mg em embalagens com 30 unidades. <bold>USO ADULTO. VENDA SOB PRESCRI&#199;&#195;O M&#201;DICA.</bold> Para maiores informa&#231;&#245;es, consulte a bula completa do produto (cit08a). Documenta&#231;&#227;o cient&#237;fica e informa&#231;&#245;es adicionais est&#227;o &#224; disposi&#231;&#227;o da classe m&#233;dica mediante solicita&#231;&#227;o. Laborat&#243;rios Pfizer Ltda., Rua Alexandre Dumas, 1860 &#150; Ch&#225;cara Santo Ant&#244;nio, S&#227;o Paulo, SP &#150; CEP 04717-904. Tel.: 0800-16-7575 &#150; Internet: <ext-link ext-link-type="uri" xlink:href="http://www.pfizer.com.br">www.pfizer.com.br</ext-link>. <bold>Citalor<sup>&#174;</sup> Reg. MS - 1. 0216.0062</bold>   </p>
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