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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">gjNk7P8BdpB8hVTTQCLxBwr</article-id>
      <article-id pub-id-type="other">00007</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2008000500007</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(08)09000507</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2008000500007</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Tratamento da persist&#234;ncia de canal arterial em rec&#233;m-nascidos prematuros: an&#225;lise cl&#237;nica e cir&#250;rgica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Locali</surname>
            <given-names>Rafael Fagionato</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Matsuoka</surname>
            <given-names>Priscila Katsumi</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gabriel</surname>
            <given-names>Edmo Atique</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bertini J&#250;nior</surname>
            <given-names>Ayrton</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>La Rotta</surname>
            <given-names>Carlos Arnulfo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Catani</surname>
            <given-names>Roberto</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carvalho</surname>
            <given-names>Ant&#244;nio Carlos de Camargo</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buffolo</surname>
            <given-names>Enio</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal de S&#227;o Paulo</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>05</month>
        <year>2008</year>
      </pub-date>
      <volume>90</volume>
      <issue>5</issue>
      <fpage>345</fpage>
      <lpage>349</lpage>
      <history>
        <date date-type="accepted">
          <day>22</day>
          <month>01</month>
          <year>2008</year>
        </date>
        <date date-type="received">
          <day>02</day>
          <month>09</month>
          <year>2007</year>
        </date>
        <date date-type="rev-recd">
          <day>20</day>
          <month>12</month>
          <year>2007</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>FUNDAMENTO: O tratamento cir&#250;rgico da persist&#234;ncia de canal arterial &#233; indicado quando a interven&#231;&#227;o cl&#237;nica fracassa. No entanto, esse tratamento n&#227;o &#233; livre de complica&#231;&#245;es. OBJETIVO: Analisar aspectos cl&#237;nicos e cir&#250;rgicos envolvidos no tratamento da persist&#234;ncia do canal arterial, em rec&#233;m-nascidos prematuros. M&#201;TODOS: No per&#237;odo de janeiro de 2000 a junho de 2006, foram analisados 22 rec&#233;m-nascidos prematuros submetidos a tratamento cir&#250;rgico para persist&#234;ncia de canal arterial. Do total de pacientes, 77,3% eram do sexo feminino, com peso m&#233;dio ao nascimento de 952,5 g e idade gestacional m&#233;dia de 27 semanas. O uso de agentes vasoativos, indometacina, par&#226;metros ecocardiogr&#225;ficos e complica&#231;&#245;es, nos per&#237;odos pr&#233; e p&#243;s-operat&#243;rios, foi avaliado. RESULTADOS: Na casu&#237;stica avaliada, 59,1% dos pacientes necessitaram de intuba&#231;&#227;o orotraqueal ao nascimento; 77,3%, de surfactante; e 59,1% usaram agentes vasoativos no pr&#233;-operat&#243;rio. O n&#250;mero m&#233;dio de aplica&#231;&#245;es de indometacina foi de 3,4, com dosagem variando de 0,1 a 0,25 mg/kg/dia. O calibre m&#233;dio do canal arterial foi de 1,96 mm. O procedimento cir&#250;rgico foi realizado por abordagem extrapleural em 59,1% dos casos, e no p&#243;s-operat&#243;rio o tempo m&#233;dio de intuba&#231;&#227;o foi de 30,9 dias, com emprego de agentes vasoativos em 50% dos pacientes. Observaram-se 18,1% de complica&#231;&#245;es p&#243;s-operat&#243;rias n&#227;o-fatais. CONCLUS&#195;O: Mais da metade dos pacientes necessitou de intuba&#231;&#227;o orotraqueal ao nascimento, emprego de surfactante e agentes vasoativos no per&#237;odo pr&#233;-operat&#243;rio. Houve maior preval&#234;ncia de abordagem extrapleural durante o ato operat&#243;rio. No per&#237;odo p&#243;s-operat&#243;rio, houve menor demanda de agentes vasoativos e n&#227;o houve &#243;bitos diretamente relacionados ao procedimento cir&#250;rgico.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Persist&#234;ncia do conduto arterioso</kwd>
        <kwd>prematuro</kwd>
        <kwd>cardiopatias cong&#234;nitas</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>27</day>
        <month>05</month>
        <year>2008</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>ARTIGO ORIGINAL </p>
    <p>
      <bold>Tratamento da persist&#234;ncia de canal arterial em rec&#233;m-nascidos prematuros: an&#225;lise cl&#237;nica e cir&#250;rgica</bold>
    </p>
    <p>
      <bold>Rafael Fagionato Locali; Priscila Katsumi Matsuoka; Edmo Atique Gabriel; Ayrton Bertini J&#250;nior; Carlos Arnulfo La Rotta; Roberto Catani; Ant&#244;nio Carlos de Camargo Carvalho; Enio Buffolo</bold>
    </p>
    <p>Universidade Federal de S&#227;o Paulo (Unifesp) - S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> O tratamento cir&#250;rgico da persist&#234;ncia de canal arterial &#233; indicado quando a interven&#231;&#227;o cl&#237;nica fracassa. No entanto, esse tratamento n&#227;o &#233; livre de complica&#231;&#245;es. </p>
    <p><bold>OBJETIVO:</bold> Analisar aspectos cl&#237;nicos e cir&#250;rgicos envolvidos no tratamento da persist&#234;ncia do canal arterial, em rec&#233;m-nascidos prematuros. </p>
    <p><bold>M&#201;TODOS:</bold> No per&#237;odo de janeiro de 2000 a junho de 2006, foram analisados 22 rec&#233;m-nascidos prematuros submetidos a tratamento cir&#250;rgico para persist&#234;ncia de canal arterial. Do total de pacientes, 77,3% eram do sexo feminino, com peso m&#233;dio ao nascimento de 952,5 g e idade gestacional m&#233;dia de 27 semanas. O uso de agentes vasoativos, indometacina, par&#226;metros ecocardiogr&#225;ficos e complica&#231;&#245;es, nos per&#237;odos pr&#233; e p&#243;s-operat&#243;rios, foi avaliado. </p>
    <p><bold>RESULTADOS:</bold> Na casu&#237;stica avaliada, 59,1% dos pacientes necessitaram de intuba&#231;&#227;o orotraqueal ao nascimento; 77,3%, de surfactante; e 59,1% usaram agentes vasoativos no pr&#233;-operat&#243;rio. O n&#250;mero m&#233;dio de aplica&#231;&#245;es de indometacina foi de 3,4, com dosagem variando de 0,1 a 0,25 mg/kg/dia. O calibre m&#233;dio do canal arterial foi de 1,96 mm. O procedimento cir&#250;rgico foi realizado por abordagem extrapleural em 59,1% dos casos, e no p&#243;s-operat&#243;rio o tempo m&#233;dio de intuba&#231;&#227;o foi de 30,9 dias, com emprego de agentes vasoativos em 50% dos pacientes. Observaram-se 18,1% de complica&#231;&#245;es p&#243;s-operat&#243;rias n&#227;o-fatais. </p>
    <p><bold>CONCLUS&#195;O:</bold> Mais da metade dos pacientes necessitou de intuba&#231;&#227;o orotraqueal ao nascimento, emprego de surfactante e agentes vasoativos no per&#237;odo pr&#233;-operat&#243;rio. Houve maior preval&#234;ncia de abordagem extrapleural durante o ato operat&#243;rio. No per&#237;odo p&#243;s-operat&#243;rio, houve menor demanda de agentes vasoativos e n&#227;o houve &#243;bitos diretamente relacionados ao procedimento cir&#250;rgico.</p>
    <p><bold>Palavras-chave:</bold> Persist&#234;ncia do conduto arterioso, prematuro, cardiopatias cong&#234;nitas.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>O canal arterial, na vida intra-&#250;tero, comporta-se como um conduto arterial vital para o satisfat&#243;rio desenvolvimento do feto, uma vez que desvia mais da metade do d&#233;bito card&#237;aco para a circula&#231;&#227;o sist&#234;mica e umbilico-placental<sup>1,2</sup>. Ao nascimento, ante a eleva&#231;&#227;o sang&#252;&#237;nea da press&#227;o de oxig&#234;nio, ocorre a constri&#231;&#227;o desse canal, concomitantemente &#224; dilata&#231;&#227;o da circula&#231;&#227;o pulmonar, estabelecendo, dessa forma, um novo padr&#227;o circulat&#243;rio no rec&#233;m-nascido (RN)<sup>1,2</sup>.</p>
    <p>Em RN prematuros, no entanto, esse mecanismo de fechamento do canal arterial n&#227;o ocorre em cerca de 50% dos casos, culminando no defeito card&#237;aco cong&#234;nito denominado persist&#234;ncia do canal arterial (PCA)<sup>1-4</sup>. Dessa maneira, ocorre um aumento do fluxo pulmonar em detrimento da perfus&#227;o sist&#234;mica, em raz&#227;o do <italic>shunt</italic> esquerdo-direito<sup>4</sup><sub>.</sub> Essa altera&#231;&#227;o hemodin&#226;mica provoca sobrecarga ventricular esquerda, disfun&#231;&#227;o mioc&#225;rdica e insufici&#234;ncia respirat&#243;ria<sup>4</sup>. Al&#233;m disso, complica&#231;&#245;es graves dependentes ou concomitantes ao PCA s&#227;o enterocolite necrotizante, insufici&#234;ncia renal, displasia broncopulmonar e hemorragia intraventricular<sup>4-10</sup>.</p>
    <p>A terap&#234;utica cl&#237;nica do PCA se baseia, especialmente, na administra&#231;&#227;o de indometacina, agente inibidor da s&#237;ntese de prostaglandinas, associado &#224; restri&#231;&#227;o de flu&#237;dos e diur&#233;ticos<sup>4</sup>. Entretanto, nas situa&#231;&#245;es que o PCA &#233; refrat&#225;rio ao manejo cl&#237;nico, &#233; indicada a sua ligadura cir&#250;rgica, com o intuito de atenuar suas complica&#231;&#245;es hemodin&#226;micas<sup>4,11-13</sup>. Apesar de essa interven&#231;&#227;o apresentar resultados satisfat&#243;rios, ela n&#227;o est&#225; livre de complica&#231;&#245;es. Portanto, o objetivo desse estudo &#233; evidenciar aspectos cl&#237;nicos e cir&#250;rgicos envolvidos no tratamento do PCA em RN prematuros.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Realizou-se uma an&#225;lise retrospectiva dos aspectos cl&#237;nicos e cir&#250;rgicos de 22 prematuros com idade gestacional inferior a 32 semanas que foram submetidos a tratamento cir&#250;rgico da persist&#234;ncia do canal arterial, durante o per&#237;odo de janeiro de 2000 at&#233; junho de 2006. Esses pacientes eram provenientes da Universidade Federal de S&#227;o Paulo &#150; Hospital S&#227;o Paulo e Hospital Santa Catarina. Foram exclu&#237;dos todos os RN portadores, concomitantemente, de outras doen&#231;as cong&#234;nitas do cora&#231;&#227;o e aqueles cujos prontu&#225;rios estavam incompletos.</p>
    <p>Dos pacientes inclu&#237;dos, cinco (22,7%) eram do sexo masculino, e 17 (77,3%), do feminino, e possu&#237;am, ao nascimento, idade gestacional m&#233;dia de 27 semanas (23 a 32 semanas) e peso m&#233;dio de 952,5 g (485&#150;1.765 g). O parto normal ocorreu em quatro (18,1%) dos pacientes, e o diagn&#243;stico da persist&#234;ncia do canal arterial foi realizado clinicamente em oito (36,3%) dos casos, e pelo ecocardiograma, em 14 (63,7%).</p>
    <p>O di&#226;metro m&#233;dio do canal arterial foi de 1,96 mm (0,2&#150;3,2 mm). De todos os pacientes, em apenas quatro (18,1%) n&#227;o foi realizado o manejo cl&#237;nico com indometacina, visto que a condi&#231;&#227;o cl&#237;nica desses pacientes exigiu abordagem cir&#250;rgica imediata. O n&#250;mero m&#233;dio de aplica&#231;&#245;es de indometacina foi de 3,4, com dosagem variando de 0,1 a 0,25 mg/kg/dia, administrados por via oral. Entretanto, em nenhum caso dessa s&#233;rie cir&#250;rgica esse medicamento foi eficaz no fechamento do canal.</p>
    <p>A partir dos documentos revisados, foram extra&#237;das informa&#231;&#245;es dos tempos pr&#233;, intra e p&#243;s-operat&#243;rios de cada paciente. Esses dados inclu&#237;ram a necessidade de intuba&#231;&#227;o orotraqueal (EOT) e par&#226;metros ventilat&#243;rios, administra&#231;&#227;o de surfactante, uso de agentes vasoativos, via de abordagem e t&#233;cnica cir&#250;rgica, complica&#231;&#245;es p&#243;s-operat&#243;rias, re-opera&#231;&#245;es, tempo de interna&#231;&#227;o hospitalar e &#243;bitos. Todos esses par&#226;metros revisados foram avaliados sob o aspecto de an&#225;lises de preval&#234;ncia.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>O procedimento cir&#250;rgico foi realizado exclusivamente no centro cir&#250;rgico, com o paciente sob anestesia geral. O acesso cir&#250;rgico de escolha foi a toracotomia p&#243;stero-lateral esquerda, e a abordagem intrapleural foi empregada em nove (40,9%) pacientes, com tempo m&#233;dio de opera&#231;&#227;o de 58 minutos (20&#150;120 minutos). Dessa s&#233;rie, apenas um paciente foi submetido a clipagem do canal arterial, sendo os outros submetidos &#224; ligadura desse canal.</p>
    <p>As complica&#231;&#245;es observadas nessa casu&#237;stica foram a displasia broncopulmonar em dois pacientes, insufici&#234;ncia card&#237;aca congestiva e infec&#231;&#227;o na ferida cir&#250;rgica em um paciente. N&#227;o foram observados casos de insufici&#234;ncia renal e enterocolite necrotizante; entretanto, todos os pacientes apresentaram hemorragia intraventricular, por&#233;m sem repercuss&#245;es no sistema nervoso central. Ocorreram tr&#234;s &#243;bitos n&#227;o relacionados ao procedimento cir&#250;rgico, em raz&#227;o de choque s&#233;ptico com foco infeccioso pulmonar, e um paciente necessitou de re-opera&#231;&#227;o por causa da soltura da clipagem. O tempo m&#233;dio de intuba&#231;&#227;o orotraqueal durante a interna&#231;&#227;o foi de 30,9 dias (1&#150;91 dias), e o tempo de interna&#231;&#227;o hospitalar m&#233;dio, de 89 dias (17&#150;332 dias). O dreno tor&#225;cico nos pacientes com abordagem intrapleural foi retirado, em m&#233;dia, 1,8 dia (1&#150;2 dias) ap&#243;s a cirurgia. A seguir, dados complementares dos resultados s&#227;o apresentados nos <xref ref-type="fig" rid="graf1">gr&#225;ficos 1</xref> e <xref ref-type="fig" rid="graf2">2</xref>.</p>
    <fig id="graf1">
      <graphic xlink:href="1678-4170-abc-90-05-0345-00007-gf01.jpg"/></fig>
    <fig id="graf2">
      <graphic xlink:href="1678-4170-abc-90-05-0345-00007-gf02.jpg"/></fig>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>A diminui&#231;&#227;o das taxas de mortalidade de RN prematuros e com baixo peso &#233; um dos marcos da medicina moderna, e reflete a evolu&#231;&#227;o e a qualidade da assist&#234;ncia a gravidez e manejo do parto. Sabe-se que o paciente prematuro, mesmo livre de outras morbidades, apresenta um retardado desenvolvimento neuropsicomotor (DNPM), devendo, por isso, possuir um acompanhamento rigoroso da equipe de sa&#250;de<sup>14</sup>.</p>
    <p>Sabe-se tamb&#233;m, no entanto, que esse grupo de pacientes apresenta um risco aumentado de malforma&#231;&#245;es e doen&#231;as cong&#234;nitas, especialmente cardiovasculares. O estudo de Rivera e cols.<sup>15</sup>, publicado em 2007, revela uma preval&#234;ncia de doen&#231;a cong&#234;nita do cora&#231;&#227;o de 13,2:1000 rec&#233;m-nascidos vivos, superior aos registros de Guitti<sup>16</sup>, de 2000, o qual apresentou 5,5:1000 nascidos vivos. Em prematuros, a presen&#231;a de doen&#231;a card&#237;aca prejudica sensivelmente o DNPM, al&#233;m do ganho p&#244;ndero-estatural da crian&#231;a. &#201; desse prisma que se deve analisar a persist&#234;ncia do canal arterial.</p>
    <p>A nossa casu&#237;stica mostra grande predomin&#226;ncia do sexo feminino (77,3%), o que corresponde com a preval&#234;ncia do PCA descrita na literatura. Em raz&#227;o da imaturidade pulmonar, foi administrado surfactante para 77,3% dos pacientes, e foi realizada intuba&#231;&#227;o orotraqueal em 59,1% dos casos. Sabe-se que o PCA influencia na adequada fun&#231;&#227;o pulmonar; entretanto, Van Woerkom e cols., em an&#225;lise de RN de baixo peso submetidos &#224; ligadura de PCA, n&#227;o encontraram melhora, em curto prazo, nos par&#226;metros ventilat&#243;rios dos doentes<sup>17</sup>. Esse fato foi confirmado por Carboni e Ringel<sup>18</sup>, Farstad e Bratlid<sup>19</sup> em seus resultados.</p>
    <p>O di&#226;metro m&#233;dio do PCA foi de 1,96 mm. Dados da literatura apontam que a gravidade do PCA pode ser expressa por uma rela&#231;&#227;o entre os tamanhos do &#225;trio esquerdo e raiz da aorta maior que 1,47, ou um di&#226;metro transverso do canal maior que 1,5 mm, na vig&#234;ncia de <italic>shunt</italic> esquerdo-direito<sup>20,21</sup>. Dessa forma, a maior parte dos pacientes deste estudo apresentava doen&#231;a com importante repercuss&#227;o cl&#237;nica e/ou hemodin&#226;mica. Por&#233;m, os pacientes com di&#226;metro transverso inferior a 1,5 mm, apesar de n&#227;o possu&#237;rem PCA grave, segundo os crit&#233;rios mencionados, apresentavam condi&#231;&#245;es cl&#237;nicas desfavor&#225;veis que os tornavam de risco elevado tamb&#233;m.</p>
    <p>O n&#250;mero de doses de indometacina empregado neste estudo condiz com doses administradas em outros estudos<sup>4,22</sup>. Por&#233;m, n&#227;o foi observado o fechamento do canal arterial seguindo esse protocolo de tratamento. O que pode explicar esse fato &#233; a administra&#231;&#227;o, neste estudo, da indometacina por via oral, comprovadamente menos eficaz que a indometacina intravenosa.</p>
    <p>Al&#233;m disso, esse agente tem sido pesquisado, tamb&#233;m, para profilaxia da hemorragia intraventricular em pacientes com PCA<sup>23,24</sup>. Uma metan&#225;lise estruturada por Fowlie e cols. em 2003<sup>14</sup> mostraram efic&#225;cia da indometacina em prevenir essa complica&#231;&#227;o. No entanto, discute-se se o efeito profil&#225;tico na hemorragia intraventricular &#233; secund&#225;ria ao fechamento do PCA pela indometacina<sup>22</sup>.</p>
    <p>Todos os pacientes apresentaram hemorragia intraventricular, fato que, na literatura, associa-se &#224; presen&#231;a de PCA<sup>4-10</sup>. Por&#233;m, esse fato pode advir, simplesmente, da prematuridade <italic>per si</italic>, uma vez que esse grupo de pacientes &#233; mais suscet&#237;vel a esse tipo de les&#227;o cerebral, independentemente de outras morbidades<sup>14</sup>. Dessa forma, concordamos com os resultados de Brooks e cols.<sup>22</sup>, quando discutem n&#227;o terem encontrado associa&#231;&#227;o entre o PCA e a hemorragia intraventricular e outras comorbidades.</p>
    <p>O procedimento operat&#243;rio, em todos os pacientes, foi realizado no centro cir&#250;rgico, sem intercorr&#234;ncias. Sabe-se que essa cirurgia pode ser realizada na unidade de terapia intensiva (UTI); por&#233;m, os riscos de infec&#231;&#227;o e de complica&#231;&#245;es, inerentes &#224; interven&#231;&#227;o operat&#243;ria, s&#227;o, de fato, mais bem controlados e evitados no centro cir&#250;rgico<sup>4</sup>. Resultados semelhantes foram relatados por Gould e cols.<sup>4</sup> em estudo que compararam a interven&#231;&#227;o realizada na unidade de terapia intensiva (UTI) com a realizada no centro cir&#250;rgico<sup>4</sup>. O embasamento para tal foi avaliar as poss&#237;veis complica&#231;&#245;es inerentes ao transporte do RN para a sala de opera&#231;&#227;o.</p>
    <p>Al&#233;m da cirurgia convencional, ou seja, a toracotomia p&#243;stero-lateral esquerda ou axilar com ligadura do canal, podem-se empregar a toracoscopia, a minitoracotomia com acesso extrapleural e o cateterismo intervencionista<sup>25-30</sup>. De fato, o desenvolvimento de diversas t&#233;cnicas para tratamento do PCA visa ao menor traumatismo, risco, custo e maior efetividade que o tratamento convencional.</p>
    <p>A abordagem extrapleural &#233; a via de escolha para a abordagem do canal arterial, uma vez que evita a necessidade da introdu&#231;&#227;o de dreno tor&#225;cico e, portanto, confere um menor risco de infec&#231;&#227;o e dor no p&#243;s-operat&#243;rio. No entanto, considerando a variabilidade anat&#244;mica da espessura da pleura parietal, por mais minuciosa que seja a dissec&#231;&#227;o, muitas vezes n&#227;o &#233; poss&#237;vel preservar sua integridade, e a via intrapleural &#233; seguida.</p>
    <p>O dreno tor&#225;cico, nas situa&#231;&#245;es em que foi empregado, permaneceu em nossos doentes por um per&#237;odo m&#233;dio de 1,8 dia. Esse dado &#233; semelhante ao descrito no estudo de Gould e cols.<sup>4</sup>. Por&#233;m, n&#227;o &#233; discutido, no estudo desse autor, o tipo de abordagem cir&#250;rgica, intra ou extrapleural, empregada.</p>
    <p>Das complica&#231;&#245;es p&#243;s-operat&#243;rias observadas, a principal foi a displasia broncopulmonar, a qual se apresenta como evento decorrente da presen&#231;a de PCA, apesar de alguns estudos n&#227;o mostrarem essa associa&#231;&#227;o<sup>4,20</sup>. Os &#243;bitos descritos n&#227;o foram decorrentes do procedimento operat&#243;rio, uma vez que ocorreram 30 dias ap&#243;s a interven&#231;&#227;o, mas refletem a gravidade do quadro do RN. A mortalidade de 13,6% corrobora com a literatura, com dados semelhantes<sup>4,20</sup>.</p>
    <p>Em resumo, os dados apresentados refletem a experi&#234;ncia do nosso servi&#231;o no tratamento do PCA, explicitando o manejo cl&#237;nico e cir&#250;rgico. De fato, os crit&#233;rios de inclus&#227;o s&#227;o restritos e bem delimitados, de maneira que se perde em n&#250;mero de pacientes, mas se ganha em homogeneidade de amostra. Entretanto, &#233; importante ressaltar, como nossa experi&#234;ncia demonstra, que, ante um paciente prematuro com PCA, estaremos, via de regra, ante um p&#243;s-operat&#243;rio hospitalar prolongado, com m&#233;dia de intuba&#231;&#227;o superior a tr&#234;s semanas, e, portanto, com risco maior de infec&#231;&#245;es hospitalares e sepse.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <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>
    <p>
      <fn id="back" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Rafael Fagionato Locali </p>
        <p> Rua 3 de maio, 130/183, Vila Clementino </p>
        <p> 04044-020, S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="rafael.locali@hotmail.com">rafael.locali@hotmail.com</email>
        </p>
      </fn>
    </p>
    <p>Artigo enviado em 02/09/2007; revisado recebido em 20/12/2007; aceito em 22/01/2008.</p>
  </body>
  <back>
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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">Patent ductus arteriosus treatment in the premature newborn: clinical and surgical analisys</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: The surgical treatment of patency ductus arteriosus is indicated when the clinical intervention fails. However, this treatment may have some complications. OBJECTIVE: To analyze clinical and surgical aspects involved on the treatment of patency ductus arteriosus in premature newborn. METHODS: Twenty two premature newborns, submitted to surgical treatment for patency ductus arteriosus from January, 2000 to June, 2006, were evaluated. There were 77,3% female patients, the mean birth weight was 952,5g and the mean gestational age was 27 weeks. The use of vasoactive drugs, indometacin, echocardiograph parameters and complications, in the pre and postoperative periods were evaluated. RESULTS: In this casuistic 59,1% patients needed intratracheal intubation at birth, 77,3% needed surfactants, 59,1% used vasoactive drugs preoperative. The mean doses of indometacin were 3,43, with dose range 0,1 to 0,25 mg/Kg/day. The mean caliber of arterial duct patent was 1,96 mm. The surgical procedure was carried out through extrapleural approach in 59.1% of the patients, the mean time of postoperative intubation was 30,9 days, and 50% of the patients used vasoactive drugs postoperative. There were 18,1% postoperative complications (postoperative non-fatal complications). CONCLUSION: More than the half of the patients needed intratracheal intubation at birth, surfactant use and vasoactive drugs in the preoperative period. There was greater prevalence of the extrapleural approach during the surgery. In the postoperative period, there was less demand of vasoactive use and there was not deaths related to the surgical procedure.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Ductus arteriosus, patent</kwd>
        <kwd>infant, premature</kwd>
        <kwd>heart defects, congenital</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>
        <fn id="top-body2">
          <label>
            <bold>Patent ductus arteriosus treatment in the premature newborn: clinical and surgical analysis</bold>
          </label>
          <p>
            <bold>Rafael Fagionato Locali; Priscila Katsumi Matsuoka; Edmo Atique Gabriel; Ayrton Bertini J&#250;nior; Carlos Arnulfo La Rotta; Roberto Catani; Ant&#244;nio Carlos de Camargo Carvalho; Enio Buffolo</bold>
          </p>
        </fn>
      </p>
      <p>Universidade Federal de S&#227;o Paulo (Unifesp) - S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing address</p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND:</bold> The surgical treatment of patent ductus arteriosus is indicated when the clinical intervention fails. However, this treatment may present some complications.</p>
      <p><bold>OBJECTIVE:</bold> To analyze clinical and surgical aspects involved in the treatment of patent ductus arteriosus in the premature newborn.</p>
      <p><bold>METHODS:</bold> Twenty-two premature newborns, submitted to surgical treatment for patent ductus arteriosus from January 2000 to June 2006, were evaluated. Of the 22 newborns, 77.3% were females, mean birth weight was 952.5 g and the mean gestational age was 27 weeks. The use of vasoactive drugs, indomethacin, echocardiographic parameters and complications were evaluated in the pre- and postoperative periods.</p>
      <p><bold>RESULTS:</bold> In this sample, 59.1% of the patients needed intratracheal intubation at birth, 77.3% needed surfactants and 59.1% used preoperative vasoactive drugs. The mean number of indomethacin doses was 3.43, with dose ranging from 0.10 to 0.25 mg/Kg/day. The mean caliber of the patent ductus arteriosus was 1.96 mm. The surgical procedure was carried out through extrapleural access in 59.1% of the patients; the mean time of postoperative intubation was 30.9 days and 50% of the patients used postoperative vasoactive drugs. There were 18.1% of postoperative complications (non-fatal postoperative complications).</p>
      <p><bold>CONCLUSION:</bold> More than 50% of the patients needed intratracheal intubation at birth, surfactant use and vasoactive drugs in the preoperative period. There was a higher prevalence of the extrapleural approach during surgery. In the postoperative period, there was a lower need for vasoactive drugs and there were no deaths related to the surgical procedure.</p>
      <p><bold>Key words:</bold> Ductus arteriosus, patent; infant, premature; heart defects, congenital.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>The arterial canal functions as a vital arterial conduit during intrauterine life that is vital for the satisfactory development of the fetus, as it diverts more than half of the cardiac output for the systemic and the umbilical-placental circulation<sup>1,2</sup>. At birth, in the presence of the blood rise of the oxygen pressure, a constriction of this canal occurs, concomitantly with the dilation of the pulmonary circulation, thus establishing a new circulatory pattern in the newborn (NB)<sup>1,2</sup>.</p>
      <p>However, in premature NB, this mechanism of arterial canal closing does not occur in 50% of the cases, resulting in a congenital cardiac defect called patent ductus arteriosus (PDA)<sup>1-4</sup>. Therefore, there is an increase in the pulmonary flow in detriment to the systemic perfusion, due to the left-right shunt<sup>4</sup>. This hemodynamic alteration causes a left ventricular overload, myocardial dysfunction and respiratory failure<sup>4</sup>. Additionally, severe complications that are associated or concomitant to PDA are necrotizing enterocolitis, renal failure, bronchopulmonary dysplasia and intraventricular hemorrhage<sup>4-10</sup>.</p>
      <p>The clinical therapy of PDA is mainly based on the administration of indomethacin, an agent that is a prostaglandin-synthesis inhibitor, associated to fluid restriction and diuretics<sup>4</sup>. However, in situations where the PDA is refractory to the clinical management, its surgical ligation is indicated, aiming at attenuating its hemodynamic complications<sup>4,11-13</sup>. Although this surgical intervention presents satisfactory results, it is not complication-free. Therefore, the aim of this study is to show the clinical and surgical aspects involved in the treatment of PDA in premature newborn infants.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>A retrospective analysis of the clinical and surgical aspects of 22 newborn infants, with gestational age below 32 weeks, who were submitted to the surgical treatment of patent ductus arteriosus during January 2000 to June 2006 was carried out. These patients were originally from the Federal University of S&#227;o Paulo &#150; <italic>Hospital S&#227;o Paulo</italic> and <italic>Hospital Santa Catarina</italic>. All NB that presented other concomitant heart diseases and/or incomplete medical files were excluded.</p>
      <p>Of the patients that were included in the study, 5 (22.7%) were males and 17 (77.3%) were females; the mean gestational age at birth was 27 weeks (ranging from 23 to 32 weeks) and mean weight was 952.5 g (ranging from 485 to 1,765 g). Birth by normal delivery had occurred in 4 (18.1%) cases and the diagnosis of PDA was carried out clinically in 8 (36.3%) and by echocardiogram in 14 (63.7%) cases.</p>
      <p>The mean diameter of the arterial canal was 1.96 mm (0.2 &#150; 3.2 mm). Of all the patients, only 4 (18.1%) did not undergo the clinical management with indomethacin, considering that their clinical condition required immediate surgical approach. The mean number of indomethacin applications was 3.4, with the dose varying from 0.1 to 0.25 mg/Kg/day, administered orally. However, this drug was not effective in any of the cases of this surgical series, regarding the closing of the canal.</p>
      <p>Based on the reviewed data, information on the pre-, intra- and postoperative periods of each patient were obtained. These data included the need for orotracheal intubation (OTI) and ventilation parameters, surfactant administration, use of vasoactive drugs, access pathway and surgical technique, postoperative complications, re-operations, hospital stay duration and deaths.</p>
      <p>All these reviewed parameters were evaluated under the aspect of analyses of prevalence.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>The surgical procedure was carried out exclusively at the surgical center, with the patient under general anesthesia. The surgical access of choice was the left posterolateral thoracotomy and the intrapleural approach was used in 9 (40.9%0 of the patients, with a mean operation time of 58 minutes (20 to 120 minutes). In this series, only one patient was submitted to the arterial canal clamping, whereas the others were submitted to its ligation.</p>
      <p>The complications observed in this series were bronchopulmonary dysplasia in 2 patients, congestive heart failure and surgical wound infection in 1 patient. No cases of renal failure or necrotizing enterocolitis were observed; however, all patients presented intraventricular hemorrhage, although there were no consequences for the central nervous system. Three deaths, which were unrelated to the surgical procedure, occurred due to septic shock with a pulmonary infectious source and 1 patient needed to be re-operated due to clamping loosening. The mean time of OTI during the hospital stay was 30.9 days (1 to 91 days) and the mean duration of hospital stay was 89 days (17 to 332 days). The chest drain in the patients with an intrapleural approach was removed after a mean time of 1.8 days (1 to 2 days) after the surgery. Complementary data of the results are shown in <xref ref-type="fig" rid="cha1-body2">charts 1</xref> and <xref ref-type="fig" rid="cha2-body2">2</xref>.</p>
      <fig id="cha1-body2">
        <graphic xlink:href="1678-4170-abc-90-05-0345-00007-gf01-en.jpg"/></fig>
      <fig id="cha2-body2">
        <graphic xlink:href="1678-4170-abc-90-05-0345-00007-gf02-en.jpg"/></fig>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The decrease in the mortality rates of premature, low-weight newborn infants is one of the milestones of modern Medicine and reflects the development and the quality of assistance given during the pregnancy and labor management. It is known that a premature patient, even when free of other comorbidities, presents neuropsychomotor development (NPMD) retardation, which requires a stringent follow-up by the healthcare team<sup>14</sup>.</p>
      <p>However, it is also known that this group of patients presents an increased risk of malformations and congenital diseases, mainly cardiovascular ones. The study by Rivera et al<sup>15</sup>, published in 2007, shows a prevalence of congenital heart disease of 13.2:1,000 live births, which is higher than that reported by Guitti<sup>16</sup>, in 2000, of 5.5:1,000 live births. In premature infants, the presence of heart disease significantly impairs the NPMD, in addition to failure to thrive. It is under these considerations that one must analyze the patent ductus arteriosus.</p>
      <p>Our cohort shows a predominance of the female sex 977.3%), which corresponds with the prevalence of PDA described in the literature. Due to lung immaturity, surfactant was administered to 77.3% of the patients and OTI was carried out in 59.1% of the cases. It is known that PDA influences adequate pulmonary function; however, Van Woerkom et al, in a study of low-weight NB infants submitted to PDA ligation, did not observe short-term improvement in the patients' ventilation parameters<sup>17</sup>. This fact was confirmed by Carboni &amp; Ringel<sup>18</sup>, Farstad &amp; Bratlid<sup>19</sup> in their results.</p>
      <p>The mean diameter of the PDA was 1.96 mm. Literature data show that PDA severity can be expressed as a ratio between the sizes of the left atrium and aortic root &gt; 1.47 or a transversal diameter of the largest canal &gt; 1.5 mm, in the presence of a left-right shunt<sup>20,21</sup>.</p>
      <p>Therefore, most of the patients in the present study presented disease with important clinical and/or hemodynamic implication. However, the patients with a transversal diameter &lt; 1.5 mm, although they did not have severe PDA, according to the aforementioned criteria, presented unfavorable clinical conditions, which also represented high risk.</p>
      <p>The number of doses of indomethacin used in this study is in accordance with the doses administered in other studies<sup>4,22</sup>. However, the closing of the arterial canal was not observed following this treatment protocol. This might be explained by the fact that, in the present study, indomethacin was administered orally, which has been proven to be less effective than the intravenous administration of the drug.</p>
      <p>Additionally, this drug has also been studied as prophylaxis for intraventricular hemorrhage in patients with PDA<sup>23,24</sup>. A meta-analysis designed by Fowlie et al, in 2003<sup>14</sup>, showed the efficacy of indomethacin in preventing this complication. Nevertheless, whether the prophylactic effect in intraventricular hemorrhage is secondary to the closing of PDA by indomethacin is debatable<sup>22</sup>.</p>
      <p>All of the patients presented intraventricular hemorrhage, a fact that, in literature, is associated to the presence of PDA<sup>4-10</sup>. However, this fact might be simply due to prematurity itself, as this group of patients is more susceptible to this type of brain injury, regardless of other morbidities<sup>14</sup>. Hence, we agree with the results by Brooks et al<sup>22</sup>, when they state they did not observe an association between PDA and intraventricular hemorrhage and other comorbidities.</p>
      <p>The surgical procedure was carried out at the surgical center, in all patients, without any intercurrent events. It is known that this surgical procedure can be performed at the Intensive Care Unit (ICU); however, the risks of infection and complications, which are inherent to the operative intervention, are in fact better controlled and prevented at the surgical center<sup>4</sup>. Similar results were reported by Gould et al<sup>4</sup>, in a study where the authors compared interventions performed at the ICU and those performed at the surgical center<sup>4</sup>. The study results were based on the possible complications inherent to the transportation of the NB to the operating room.</p>
      <p>In addition to the conventional surgery, i.e., the left posterolateral or axillary thoracotomy with canal ligation, the thoracoscopy can be employed, as well as the mini-thoracotomy with extrapleural access and the interventionist catheterism<sup>25-30</sup>.</p>
      <p>In fact, the development of several techniques for the treatment of PDA aims at attaining the least trauma, risk, cost and higher effectiveness than the conventional treatment.</p>
      <p>The extrapleural approach is the access of choice for reaching the arterial canal, as it prevents the need for introducing a chest drain and thus, results in a lower risk of postoperative infection and pain. However, considering the anatomical variability of the parietal pleural thickness, even when the dissection is performed very carefully, many times it is not possible to preserve its integrity and the intrapleural access is followed.</p>
      <p>The chest drain, when employed, remained in our patients for a mean period of 1.8 days. This is in accordance with the information reported by Gould et al<sup>4</sup>. However, these authors do not discuss the type of surgical access was employed, whether it was intra or extrapleural.</p>
      <p>Among the observed postoperative complications, the main one was bronchopulmonary dysplasia, which presented as a consequence of the PDA, although some studies do not show such association<sup>4,20</sup>. The deaths described were not due to the surgical procedure, as they occurred 30 days after the intervention, but they reflect the severity of the picture in the newborn. The mortality rate of 13.6% is in accordance with that reported in literature, with similar data<sup>4,20</sup>.</p>
      <p>In summary, the data presented here show the experience of our Service in the treatment of PDA, explicating the clinical and surgical management. In fact, the inclusion criteria are restricted and well-delimited, so if anything is lost regarding the number of patients, it is gained in terms of sample homogeneity. However, it is important to mention that, as demonstrated by our experience, when treating a newborn patient with PDA, one must keep in mind that a prolonged postoperative period should be expected, with a mean intubation time &gt; 3 weeks and, therefore, with a higher risk of hospital infection and sepsis.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
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