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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">sZpjRkVRhjckVnMR3HyVbVM</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2012001100006</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(12)09900206</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2012005000062</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Felipressina aumenta press&#227;o arterial durante procedimento odontol&#243;gico em pacientes hipertensos</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Bronzo</surname>
            <given-names>Ana L&#250;cia Aparecida</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cardoso Jr.</surname>
            <given-names>Crivaldo Gomes</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ortega</surname>
            <given-names>K&#225;tia Coelho</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mion Jr</surname>
            <given-names>D&#233;cio</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 de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina </institution>
        <institution content-type="orgdiv2">Unidade de Hipertens&#227;o</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2012</year>
      </pub-date>
      <volume>99</volume>
      <issue>2</issue>
      <fpage>724</fpage>
      <lpage>731</lpage>
      <history>
        <date date-type="received">
          <day>23</day>
          <month>11</month>
          <year>2011</year>
        </date>
        <date date-type="accepted">
          <day>28</day>
          <month>02</month>
          <year>2012</year>
        </date>
        <date date-type="rev-recd">
          <day>23</day>
          <month>11</month>
          <year>2011</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: A felipressina foi adicionada ao anest&#233;sico local para aumentar a dura&#231;&#227;o do efeito anest&#233;sico e reduzir a toxicidade nos procedimentos dent&#225;rios. No entanto, o efeito sobre a press&#227;o arterial &#233; incerta, e isso pode ser altamente relevante no tratamento dent&#225;rio de pacientes hipertensos. OBJETIVO: Investigar o efeito da felipressina sobre a press&#227;o arterial em pacientes hipertensos com press&#227;o arterial controlada. M&#201;TODOS: Foram estudados 71 indiv&#237;duos com essas caracter&#237;sticas e com necessidade de tratamento periodontal. Ap&#243;s 10 minutos de repouso, a anestesia local (priloca&#237;na) foi infiltrada com e sem adi&#231;&#227;o de felipressina. Em seguida, uma raspagem subgengival profunda foi realizada. A press&#227;o arterial foi medida por um equipamento oscilom&#233;trico autom&#225;tico (DIXTAL DX2010). Dez minutos ap&#243;s a administra&#231;&#227;o do anest&#233;sico, o pico de a&#231;&#227;o anest&#233;sica foi gravado. O Invent&#225;rio de Ansiedade Tra&#231;o-Estado (IDATE) foi utilizado para avaliar o tra&#231;o de ansiedade nos pacientes. RESULTADOS: A press&#227;o arterial sist&#243;lica aumentou ap&#243;s a anestesia, independentemente da associa&#231;&#227;o com felipressina, durante todo o procedimento dent&#225;rio (p &lt; 0,05), e essa resposta pode ser explicada, pelo menos em parte, pelos n&#237;veis de tra&#231;o de ansiedade dos indiv&#237;duos. No entanto, um aumento adicional na press&#227;o arterial diast&#243;lica foi observado quando a priloca&#237;na foi associada a felipressina (p &lt; 0,05), mas essa resposta n&#227;o se alterou com os n&#237;veis de tra&#231;o de ansiedade. CONCLUS&#195;O: A felipressina aumentou a press&#227;o arterial diast&#243;lica de pacientes hipertensos com press&#227;o arterial controlada. Pacientes com tra&#231;o de ansiedade elevado apresentaram aumento na press&#227;o arterial sist&#243;lica em alguns procedimentos, sugerindo que um aumento da press&#227;o arterial tamb&#233;m pode estar relacionado ao medo ou &#224; ansiedade.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Felipressina</kwd>
        <kwd>press&#227;o arterial</kwd>
        <kwd>anestesia local</kwd>
        <kwd>hipertens&#227;o</kwd>
        <kwd>doen&#231;as periodontais</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>28</day>
        <month>06</month>
        <year>2012</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>Felipressina aumenta press&#227;o arterial durante procedimento odontol&#243;gico em pacientes hipertensos</bold>
    </p>
    <p>
      <bold>Ana L&#250;cia Aparecida Bronzo; Crivaldo Gomes Cardoso Jr.; K&#225;tia Coelho Ortega; D&#233;cio Mion Jr</bold>
    </p>
    <p>Unidade de Hipertens&#227;o - Disciplina de Nefrologia da Universidade de S&#227;o Paulo, Faculdade de Medicina, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="nota1">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> A felipressina foi adicionada ao anest&#233;sico local para aumentar a dura&#231;&#227;o do efeito anest&#233;sico e reduzir a toxicidade nos procedimentos dent&#225;rios. No entanto, o efeito sobre a press&#227;o arterial &#233; incerta, e isso pode ser altamente relevante no tratamento dent&#225;rio de pacientes hipertensos. </p>
    <p><bold>OBJETIVO:</bold> Investigar o efeito da felipressina sobre a press&#227;o arterial em pacientes hipertensos com press&#227;o arterial controlada. </p>
    <p><bold>M&#201;TODOS:</bold> Foram estudados 71 indiv&#237;duos com essas caracter&#237;sticas e com necessidade de tratamento periodontal. Ap&#243;s 10 minutos de repouso, a anestesia local (priloca&#237;na) foi infiltrada com e sem adi&#231;&#227;o de felipressina. Em seguida, uma raspagem subgengival profunda foi realizada. A press&#227;o arterial foi medida por um equipamento oscilom&#233;trico autom&#225;tico (DIXTAL DX2010). Dez minutos ap&#243;s a administra&#231;&#227;o do anest&#233;sico, o pico de a&#231;&#227;o anest&#233;sica foi gravado. O Invent&#225;rio de Ansiedade Tra&#231;o-Estado (IDATE) foi utilizado para avaliar o tra&#231;o de ansiedade nos pacientes. </p>
    <p><bold>RESULTADOS:</bold> A press&#227;o arterial sist&#243;lica aumentou ap&#243;s a anestesia, independentemente da associa&#231;&#227;o com felipressina, durante todo o procedimento dent&#225;rio (p &lt; 0,05), e essa resposta pode ser explicada, pelo menos em parte, pelos n&#237;veis de tra&#231;o de ansiedade dos indiv&#237;duos. No entanto, um aumento adicional na press&#227;o arterial diast&#243;lica foi observado quando a priloca&#237;na foi associada a felipressina (p &lt; 0,05), mas essa resposta n&#227;o se alterou com os n&#237;veis de tra&#231;o de ansiedade. </p>
    <p><bold>CONCLUS&#195;O:</bold> A felipressina aumentou a press&#227;o arterial diast&#243;lica de pacientes hipertensos com press&#227;o arterial controlada. Pacientes com tra&#231;o de ansiedade elevado apresentaram aumento na press&#227;o arterial sist&#243;lica em alguns procedimentos, sugerindo que um aumento da press&#227;o arterial tamb&#233;m pode estar relacionado ao medo ou &#224; ansiedade.</p>
    <p><bold>Palavras-chave:</bold> Felipressina; press&#227;o arterial; anestesia local; hipertens&#227;o; doen&#231;as periodontais.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A felipressina &#233; um horm&#244;nio sint&#233;tico do lobo posterior da hip&#243;fise, caracterizado por propriedades vasoconstritoras, amplamente utilizado em procedimentos dent&#225;rios<sup>1</sup>. Sua a&#231;&#227;o vasoconstritora parece ser mediada por receptores V1 das c&#233;lulas musculares lisas dos vasos sangu&#237;neos<sup>2</sup>. No entanto, &#233; not&#225;vel que a a&#231;&#227;o vasoconstritora mediada pelo receptor V1 &#233; dependente do territ&#243;rio, uma vez que os vasos dos m&#250;sculos esquel&#233;ticos e da pele s&#227;o mais sens&#237;veis que vasos renais<sup>2</sup>. De qualquer modo, a felipressina tem sido amplamente adicionada a solu&#231;&#245;es de anest&#233;sicos locais para aumentar a dura&#231;&#227;o do efeito anest&#233;sico e reduzir o risco de toxicidade em procedimentos dent&#225;rios<sup>3</sup>. Uma vez que os seus benef&#237;cios s&#227;o ineg&#225;veis, a sua utiliza&#231;&#227;o &#233; recomendada pelo Conselho Terap&#234;utico de Odontologia dos Estados Unidos da Am&#233;rica<sup>3</sup>, em associa&#231;&#227;o com todos os anest&#233;sicos locais, porque a aus&#234;ncia de um vasoconstritor promove a absor&#231;&#227;o r&#225;pida do anest&#233;sico e, em consequ&#234;ncia, a diminui&#231;&#227;o da efic&#225;cia do anest&#233;sico. </p>
    <p>No Brasil, onde a hipertens&#227;o afeta 22%-41% da popula&#231;&#227;o adulta<sup>4</sup>, cirurgi&#245;es-dentistas frequentemente t&#234;m de oferecer atendimento odontol&#243;gico para pacientes hipertensos. No entanto, apesar dos benef&#237;cios mencionados para os procedimentos dent&#225;rios, ainda n&#227;o &#233; claro se a adi&#231;&#227;o de felipressina &#224; priloca&#237;na aumenta a Press&#227;o Arterial (PA), especialmente em indiv&#237;duos com condi&#231;&#245;es especiais, como &#233; o caso dos pacientes hipertensos<sup>5,6</sup>. &#201; verdade que o n&#237;vel de aumento da press&#227;o arterial relacionado com a felipressina pode ser baixo; no entanto, alguns subgrupos, como os hipertensos, podem beneficiar-se de esfor&#231;os para reduzir o risco cardiovascular adicional relacionado com a felipressina. Al&#233;m disso, a escolha do anest&#233;sico local parece influenciar a resposta hemodin&#226;mica durante o procedimento dent&#225;rio<sup>7,8</sup> e, por conseguinte, na aus&#234;ncia de qualquer intera&#231;&#227;o com os receptores adren&#233;rgicos, tem sido sugerido que a felipressina apresenta uma menor incid&#234;ncia de efeitos secund&#225;rios sobre a resposta hemodin&#226;mica<sup>9</sup>. Por todas essas raz&#245;es, &#233; importante investigar o efeito da felipressina na PA em pacientes hipertensos.</p>
    <p>Outro aspecto a ser considerado &#233; a resposta individual ao estresse durante os procedimentos odontol&#243;gicos. Sabe-se que a resposta a um est&#237;mulo estressor particular &#233; maior em hipertensos que em indiv&#237;duos normotensos<sup>10</sup>. Por conseguinte, a poss&#237;vel dor causada por procedimentos dent&#225;rios sem anestesia, ou mesmo em situa&#231;&#245;es de anestesia ineficaz, pode produzir estresse no paciente, o que resulta na libera&#231;&#227;o de catecolaminas end&#243;genas, que, por vezes, atingem n&#237;veis mais elevados do que o valor agregado contido num tubo de anestesia<sup>1</sup>. Assim, os procedimentos dent&#225;rios tamb&#233;m podem aumentar a PA como resultado do medo ou da ansiedade<sup>11</sup>, al&#233;m do poss&#237;vel aumento na PA devido &#224; a&#231;&#227;o da felipressina<sup>12</sup>, especialmente em pacientes hipertensos.</p>
    <p>Trabalhamos com a hip&#243;tese de que a PA pode aumentar na presen&#231;a de felipressina durante procedimentos odontol&#243;gicos, e o objetivo deste estudo foi investigar o efeito da anestesia, associados ou n&#227;o com a felipressina sobre a PA em pacientes hipertensos, controlados farmacologicamente, durante o tratamento periodontal.</p>
    <p>
      <bold>Materiais e M&#233;todos</bold>
    </p>
    <p>O presente estudo foi aberto, randomizado, de duas vias, com dois tratamentos, dose &#250;nica, ap&#243;s duas horas de jejum, e os tratamentos foram separados por um per&#237;odo de suspens&#227;o (<italic>wash-out</italic>) de 10 minutos entre as interven&#231;&#245;es (priloca&#237;na o priloca&#237;na com felipressina) para observar o estudo cruzado proposto. A cada indiv&#237;duo foi atribu&#237;do um n&#250;mero de identifica&#231;&#227;o &#250;nico e durante todo o estudo, todos os procedimentos foram realizados pelos mesmos pesquisadores, com um protocolo padronizado. Os procedimentos foram realizados em conformidade com as orienta&#231;&#245;es da Declara&#231;&#227;o de Helsinque para experimentos com seres humanos e aprovado pelo Comit&#234; de &#201;tica do Hospital Geral da Universidade de S&#227;o Paulo, Brasil. Todos os volunt&#225;rios assinaram um termo de consentimento informado antes de sua participa&#231;&#227;o. O projeto experimental est&#225; na <xref ref-type="fig" rid="aop05912fig01">figura 1</xref>.</p>
    <p content-type="asset">
      <fig id="aop05912fig01">
        <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf01.jpg"/></fig>
    </p>
    <p>
      <bold>Indiv&#237;duos</bold>
    </p>
    <p>Foram investigados 71 pacientes hipertensos sob tratamento anti-hipertensivo e com a PA controlada, avaliada na &#250;ltima consulta m&#233;dica (PA sist&#243;lica e diast&#243;lica inferior a 140/90 mmHg, respectivamente). A amostra incluiu pacientes de ambos os sexos que necessitavam de tratamento periodontal. Os pacientes que apresentavam diabete melito, insufici&#234;ncia renal, card&#237;aca, coron&#225;ria ou insufici&#234;ncia hep&#225;tica, e mulheres gr&#225;vidas foram exclu&#237;dos.</p>
    <p>
      <bold>Avalia&#231;&#245;es preliminares</bold>
    </p>
    <p>Todos os pacientes foram submetidos a um exame inicial dental. Na chegada ao consult&#243;rio do dentista, eles foram colocados para descansar, sentados em uma cadeira de dentista confort&#225;vel com o encosto em um &#226;ngulo de 45&#186;;, por 10 minutos. Depois disso, foi avaliado o n&#237;vel de tra&#231;o de ansiedade e foram classificados como pacientes com n&#237;vel de ansiedade baixo ou elevado. Subsequentemente, o dentista realizou a avalia&#231;&#227;o da sa&#250;de bucal e verificou a presen&#231;a de doen&#231;a periodontal. Para esses efeitos, a doen&#231;a periodontal foi diagnosticada de acordo com os crit&#233;rios de &#237;ndice periodontais (Periodontal Screening &amp; Recording - PSR). Resumidamente, esse &#237;ndice identifica a presen&#231;a de inflama&#231;&#227;o gengival e fatores agravantes locais, como placa bacteriana e t&#225;rtaro atacando os tecidos gengival e periodontal<sup>13</sup>. Os pacientes que n&#227;o preencheram esses crit&#233;rios foram exclu&#237;dos. Ent&#227;o, de modo a familiariz&#225;-los com os procedimentos, todos os pacientes foram submetidos &#224; raspagem subgengival sem procedimentos anest&#233;sicos, uma vez que a raspagem subgengival n&#227;o &#233; dolorosa. </p>
    <p>
      <bold>Avalia&#231;&#227;o da ansiedade</bold>
    </p>
    <p>O Invent&#225;rio de Ansiedade Tra&#231;o-Estado (IDATE) foi utilizado para avaliar o n&#237;vel de ansiedade nos pacientes. Esse invent&#225;rio &#233; composto de duas partes, com 20 indica&#231;&#245;es cada, e determina como a pessoa geralmente se sente na vida com base em uma escala, com um escore que varia de 20 a 80. Assim, os pacientes foram classificados de acordo com sua pontua&#231;&#227;o como apresentando "baixa ansiedade" (escore menor ou igual a 25) ou "alta ansiedade" (escore acima de 25).</p>
    <p>
      <bold>Press&#227;o arterial</bold>
    </p>
    <p>Durante a sess&#227;o experimental, a PA foi medida em triplicado e calculada a m&#233;dia para cada per&#237;odo (repouso, anest&#233;sico local, raspagem subgengival e pico anest&#233;sico) com um dispositivo oscilom&#233;trico autom&#225;tico (DIXTAL - modelo DX 2010, S&#227;o Paulo, Brasil), que &#233; resultado do aperfei&#231;oamento do DIXTAL - modelo DX 2710<sup>14</sup>, validado conforme as normas internacionais<sup>15</sup>. O manguito utilizado foi do tamanho adequado para a circunfer&#234;ncia do bra&#231;o dominante do paciente: a) manguito "adulto" com bolsa infl&#225;vel de 13 x 24 cm para pacientes com circunfer&#234;ncia do bra&#231;o de 24 x 32 cm, e, b) manguito "obeso" com bolsa infl&#225;vel de 17 x 32 cm para pacientes com circunfer&#234;ncia do bra&#231;o de 32 x 42 cm. Durante a medi&#231;&#227;o, o manguito foi posicionado no bra&#231;o e ajustado para a altura do ventr&#237;culo esquerdo<sup>16</sup>. </p>
    <p>
      <bold>Tratamento periodontal</bold>
    </p>
    <p>Durante o tratamento periodontal, todos os pacientes foram instru&#237;dos a tomar os medicamentos anti-hipertensivos &#224;s 8h00, para garantir a a&#231;&#227;o anti-hipertensiva ao mesmo tempo da sess&#227;o experimental. Os pacientes chegaram ao consult&#243;rio dent&#225;rio &#224;s 14h00, ap&#243;s um per&#237;odo p&#243;s-prandial de duas horas, a fim de evitar qualquer efeito dos alimentos sobre a PA.</p>
    <p>Durante o per&#237;odo pr&#233;-interven&#231;&#227;o, definido como REPOUSO, os pacientes sentaram numa cadeira confort&#225;vel de dentista com o encosto em um &#226;ngulo de 45&#186; durante 10 minutos, durante os quais os a PA foi medida a cada dois minutos. Em seguida, o anest&#233;sico local (priloca&#237;na), com ou sem felipressina, foi infiltrado usando uma seringa com uma agulha carpule 30G. Esse procedimento foi chamado de ANESTESIA LOCAL e durou quatro minutos. As quantidades utilizadas foram 144 mg de priloca&#237;na 4% sem felipressina (2 tubos) e 108 mg de priloca&#237;na com 0,11 UI de felipressina (2 tubos), totalizando quatro tubos. Cabe ressaltar que a diferen&#231;a na quantidade de priloca&#237;na &#233; devida &#224; disponibilidade comercial do anest&#233;sico local, que s&#243; &#233; encontrado como priloca&#237;na 3% com felipressina 0,03 UI, e priloca&#237;na 4%, sem vasoconstritor. Durante esse passo, a PA foi medida duas vezes. Ap&#243;s a anestesia, for realizado o procedimento t&#233;cnico de raspagem subgengival profunda e a PA foi novamente medida a cada dois minutos. Esse procedimento dental, definido como per&#237;odo de RASPAGEM SUBGENGIVAL, &#233; sempre doloroso e justifica a utiliza&#231;&#227;o de um anest&#233;sico. O pico do anest&#233;sico priloca&#237;na ou priloca&#237;na associada felipressina foi atingido 10 minutos ap&#243;s a inje&#231;&#227;o do anest&#233;sico, e a PA foi medida duas vezes. Esse per&#237;odo foi definido como per&#237;odo de PICO DO ANEST&#201;SICO. Os instrumentos utilizados durante a raspagem subgengival profunda foram curetas McCall e Grayce, raspadores, e sondas periodontais.</p>
    <p>
      <bold>Simula&#231;&#227;o de anest&#233;sico </bold>
    </p>
    <p>Uma sub-amostra de 34 pacientes foi convidada a participar de uma sess&#227;o de simula&#231;&#227;o de anest&#233;sico, uma semana antes da sess&#227;o experimental, no qual se realizou uma simula&#231;&#227;o de anest&#233;sico com uma agulha e uma seringa vazia, a fim de avaliar o efeito do procedimento, na PA. Os detalhes da sess&#227;o de simula&#231;&#227;o do anest&#233;sico foram os seguintes: repouso, avalia&#231;&#227;o da sa&#250;de bucal e raspagem subgengival nas avalia&#231;&#245;es preliminares. Esse procedimento foi realizado uma semana antes da sess&#227;o experimental, imediatamente ap&#243;s a avalia&#231;&#227;o odontol&#243;gica para determinar a necessidade de tratamento odontol&#243;gico.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>Considerando uma pot&#234;ncia de 80% e um erro alfa de 5%, o tamanho da amostra m&#237;nima necess&#225;ria para detectar uma diferen&#231;a de 10 mmHg na PA foi calculada em 37 indiv&#237;duos.</p>
    <p>A normalidade dos dados foi verificada por meio do teste de Shapiro-Wilks, usando o pacote estat&#237;stico SPSS for Windows (Statistical Package for Social Sciences, vers&#227;o 13.0, Chicago, IL, EUA).</p>
    <p>Os efeitos da priloca&#237;na associada ou n&#227;o com a felipressina foram comparadas pelo teste ANOVA bifatorial para medidas repetidas, estabelecendo anest&#233;sico (priloca&#237;na ou priloca&#237;na + felipressina) e est&#225;gio (repouso, anestesia, raspagem subgengival e pico de anest&#233;sico) como os principais fatores. Compara&#231;&#245;es post-hoc foram feitas usando o teste de Newman-Keuls. Valores de p &lt; 0,05 foram considerados estatisticamente significativos, e os dados s&#227;o apresentados como m&#233;dia e erro padr&#227;o. O pacote de software utilizado para essas an&#225;lises foi STATISTICA (Estat&#237;stica para Windows 4. 3, StatSoft Inc, Tulsa, OK, EUA, 1993).</p>
    <p>Os resultados prim&#225;rios foram as mudan&#231;as na PA de consult&#243;rio durante os procedimentos odontol&#243;gicos dolorosos e os efeitos da priloca&#237;na associada ou n&#227;o com a felipressina.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>Setenta e um pacientes hipertensos (44 mulheres e 27 homens) com PA controlada por tratamento anti-hipertensivo e necessitando de tratamento periodontal completaram o estudo. A caracteriza&#231;&#227;o da amostra &#233; apresentada na <xref ref-type="table" rid="tab1">tabela 1</xref>. &#201; interessante notar que o tra&#231;o de ansiedade foi medido em 36 pacientes apenas, porque os outros volunt&#225;rios n&#227;o preencheram completamente os formul&#225;rios.</p>
    <table-wrap id="tab1">
      <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gt01.jpg"/></table-wrap>
    <p>Os efeitos da sess&#227;o de simula&#231;&#227;o de anest&#233;sico s&#227;o apresentados na <xref ref-type="fig" rid="aop05912fig02">figura 2</xref>.</p>
    <p content-type="asset">
      <fig id="aop05912fig02">
        <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf02.jpg"/></fig>
    </p>
    <p>Durante a sess&#227;o de simula&#231;&#227;o de anest&#233;sico, tanto a PA sist&#243;lica quanto a diast&#243;lica aumentaram significativamente (p &lt; 0,05) em compara&#231;&#227;o com as outras etapas da sess&#227;o (repouso, avalia&#231;&#227;o da sa&#250;de bucal e raspagem subgengival).</p>
    <p>A <xref ref-type="fig" rid="aop05912fig03">figura 3</xref> mostra o efeito do anest&#233;sico, com e sem felipressina, na PA. Quanto &#224; PA sist&#243;lica, foi identificado um efeito significativo do fator est&#225;gio, uma vez que a priloca&#237;na, com ou sem felipressina, aumentou a PA sist&#243;lica durante todo o per&#237;odo da consulta ao dentista (p &lt; 0,05). No entanto, em rela&#231;&#227;o &#224; PA diast&#243;lica, foi encontrada uma intera&#231;&#227;o significativa entre os principais fatores (condi&#231;&#227;o e est&#225;gio). Assim, a PA diast&#243;lica aumentou durante todos os procedimentos odontol&#243;gicos sob ambas as condi&#231;&#245;es, mas esse aumento foi maior quando o anest&#233;sico foi associada &#224; felipressina (p &lt; 0,05).</p>
    <p content-type="asset">
      <fig id="aop05912fig03">
        <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf03.jpg"/></fig>
    </p>
    <p>Em uma an&#225;lise complementar, os indiv&#237;duos com baixo (escore &lt;25) e alto (escore&gt;baixo 25) tra&#231;o de ansiedade foram comparados, e foi observado que a PA sist&#243;lica aumentou significativamente durante a anestesia e a raspagem subgengival, apenas nos pacientes com tra&#231;o de ansiedade mais alto (<xref ref-type="fig" rid="aop05912fig04">figura 4</xref>). No entanto, n&#227;o foi observada diferen&#231;a significativa na PA diast&#243;lica (p &gt; 0,05). </p>
    <p content-type="asset">
      <fig id="aop05912fig04">
        <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf04.jpg"/></fig>
    </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>A originalidade do presente estudo &#233; a constata&#231;&#227;o de que o anest&#233;sico associado a felipressina aumenta a PA diast&#243;lica de pacientes hipertensos com PA controlada farmacologicamente. </p>
    <p>Descobrimos aqui que a infus&#227;o aguda de priloca&#237;na associada a felipressina promove um aumento na PA diast&#243;lica, mas n&#227;o na sist&#243;lica. Nosso estudo est&#225; de acordo com o de Gortzak e cols.<sup>17</sup>que observaram que, em coelhos brancos japoneses machos submetidos a traqueostomia, a PA diast&#243;lica aumentou significativamente, sem altera&#231;&#227;o na PA sist&#243;lica. No entanto, o nosso estudo difere dos outros com experimenta&#231;&#227;o humana, que mostraram que a felipressina n&#227;o est&#225; associada com aumentos da PA<sup>18</sup>. Essa diferen&#231;a pode ser justificada pelo fato de que n&#243;s investigamos pacientes hipertensos com PA controlada, e o efeito da felipressina pode ser diferente em pacientes hipertensos com PA n&#227;o controlada, porque a presen&#231;a de uma PA j&#225; elevada pode mascarar a resposta da PA &#224; felipressina. Al&#233;m disso, cabe ressaltar que os receptores V1 podem desencadear uma potente resposta vasoconstritora<sup>19</sup> e isso poderia, portanto, contribuir para o controle t&#244;nico de circula&#231;&#227;o, porque os antagonistas espec&#237;ficos dos receptores V1 produzem uma ligeira, mas de longa dura&#231;&#227;o, queda na PA2. No entanto, o efeito da felipressina sobre o t&#244;nus vascular &#233; ainda uma quest&#227;o controversa.</p>
    <p>O uso de um anest&#233;sico local, associado ou n&#227;o com um vasoconstritor, no atendimento odontol&#243;gico de pacientes hipertensos e seus efeitos adversos sobre a PA, foi avaliado por v&#225;rios autores<sup>3,16,20</sup>, mas n&#227;o existem estudos conclusivos sobre esse assunto at&#233; agora. No presente estudo, identificamos uma eleva&#231;&#227;o da PA em todos os procedimentos, e uma an&#225;lise parcial dos dados mostrou que essa eleva&#231;&#227;o tende a ser mais pronunciada durante o procedimento anest&#233;sico. Assim, surgem duas hip&#243;teses: a) a priloca&#237;na tamb&#233;m aumenta a PA, e b) procedimentos odontol&#243;gicos s&#227;o suficientemente estressantes para aumentar a PA, independentemente da priloca&#237;na. Com base nessa an&#225;lise inicial, n&#243;s decidimos incluir um procedimento de simula&#231;&#227;o de anest&#233;sico com seringa vazia e agulha, de modo a monitorar a PA no momento da anestesia. Durante essa simula&#231;&#227;o, houve uma eleva&#231;&#227;o significativa na PA sist&#243;lica, sugerindo que o medo e a ansiedade podem provocar tal resposta. Na verdade, Gortzack e cols.<sup>17</sup> tamb&#233;m demonstraram uma eleva&#231;&#227;o da PA mais pronunciada durante a administra&#231;&#227;o de um anest&#233;sico local, seguida de redu&#231;&#227;o ap&#243;s a remo&#231;&#227;o da agulha.</p>
    <p>Tem sido sugerido que os betabloqueadores podem reduzir a libera&#231;&#227;o de adrenalina end&#243;gena<sup>16 </sup>e, portanto, interferir com a resposta da PA. Coincidentemente, em nosso estudo, 58% dos indiv&#237;duos estavam sob tratamento de betabloqueador, e 58% da subpopula&#231;&#227;o em que o n&#237;vel de estresse foi avaliado mostraram ansiedade leve. Por conseguinte, &#233; poss&#237;vel pensar que a utiliza&#231;&#227;o de betabloqueadores possa afetar as respostas da PA ao estresse. Assim, decidimos avaliar nossos pacientes separadamente de acordo com seu uso ou n&#227;o de betabloqueadores (dados n&#227;o mostrados). No entanto, nenhuma diferen&#231;a significativa foi encontrada na PA sist&#243;lica ou diast&#243;lica durante todo o protocolo experimental (p &gt; 0,05).</p>
    <p>Sabe-se que a resposta a um est&#237;mulo estressor particular &#233; maior em hipertensos que em indiv&#237;duos normotensos. Al&#233;m disso, vale ressaltar que entre os hipertensos existe variabilidade no &#237;ndice de estresse. Em uma subamostra de nosso estudo, 42% dos indiv&#237;duos foram classificados como indiv&#237;duos com ansiedade elevada, achou-se que a priloca&#237;na sem vasoconstritor promove um aumento da PA sist&#243;lica (<xref ref-type="fig" rid="aop05912fig04">figura 4</xref>); todavia, quando associada &#224; felipressina, essa resposta n&#227;o foi observada (p &gt; 0,05), o que sugere que a resposta da press&#227;o arterial &#224; felipressina n&#227;o &#233; influenciada pelo n&#237;vel de ansiedade.</p>
    <p>
      <bold>Conclus&#245;es</bold>
    </p>
    <p>Em conclus&#227;o, os achados indicam que a felipressina aumenta a PA diast&#243;lica, independentemente de suas propriedades anest&#233;sicas. Al&#233;m disso, um aumento significativo na PA sist&#243;lica ocorre em pacientes hipertensos, cuja PA &#233; controlada por meio de tratamento anti-hipertensivo. Pacientes com tra&#231;o de ansiedade elevado apresentaram aumento na PA sist&#243;lica em alguns procedimentos, sugerindo que um aumento da PA tamb&#233;m pode estar relacionado ao medo ou &#224; ansiedade. Finalmente, este estudo contribuiu para desvendar o risco hemodin&#226;mico que a hipertens&#227;o pode apresentar no uso de priloca&#237;na + felipressina. Contudo, n&#227;o revela se na pr&#225;tica dent&#225;ria &#233; amplamente utilizada na rotina cl&#237;nica para essa popula&#231;&#227;o.</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>Este artigo &#233; parte de tese de mestrado de Ana L&#250;cia Aparecida Bronzo pela Faculdade de Medicina da Universidade de S&#227;o Paulo (Disciplina de Nefrologia ministrada pelo Professor D&#233;cio Mion Junior).</p>
    <p>
      <fn id="nota1" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p>Crivaldo Gomes Cardoso Junior </p>
        <p> Rua Felipe Galv&#227;o Pereira, 160, Vila Lolly </p>
        <p> CEP 12460-000, Campos do Jord&#227;o, SP - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="crivaldo@gmail.com">crivaldo@gmail.com</email>, </p>
        <p>
          <email xlink:href="crivaldo@usp.br">crivaldo@usp.br </email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 23/11/11; revisado em 23/11/11; aceito em 28/02/12.</p>
  </body>
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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">Felypressin increases blood pressure during dental procedures in hypertensive patients</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Felypressin has been added to local anesthetic to increase the length of the anesthetic effect and reduce toxicity during dental procedures. However, the effect on blood pressure remains uncertain, and this may be highly relevant in the dental treatment of hypertensive patients. OBJECTIVE: To investigate the effect of felypressin on blood pressure in hypertensive patients with controlled BP. METHODS: 71 subjects with these characteristics and in need of periodontal treatment were studied. After 10 minutes of rest, local anesthesia (prilocaine) was infiltrated with and without addition of felypressin. Then, a deep subgingival scaling was performed. Blood pressure was measured by an automated oscillometric device (DIXTAL DX2010). Ten minutes after the administration of the anesthetic, peak anesthetic action was recorded. The State-Trait Anxiety Inventory (STAI) was used to assess the patients' trait anxiety. RESULTS: Systolic blood pressure increased after anesthesia, regardless of association with felypressin, throughout the dental procedure (p&lt;0.05) and this response can be explained, at least in part, by the trait anxiety levels of the subjects. However, a further increase in diastolic blood pressure was observed when prilocaine was associated with felypressin (p&lt;0.05), but this response did not change with trait anxiety levels. CONCLUSION: Felypressin increased the diastolic blood pressure of hypertensive patients with controlled blood pressure. Patients with high trait anxiety presented increases in systolic blood pressure upon some procedures, suggesting that an increase in blood pressure might also be related to fear or anxiety.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Felypressin</kwd>
        <kwd>blood pressure</kwd>
        <kwd>anesthesia, local</kwd>
        <kwd>hypertension</kwd>
        <kwd>periodontal diseases</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <fn id="nota_1-body2">
          <label>
            <bold>Felypressin increases blood pressure during dental procedures in hypertensive patients</bold>
          </label>
          <p>
            <bold>Ana L&#250;cia Aparecida Bronzo; Crivaldo Gomes Cardoso Jr.; K&#225;tia Coelho Ortega; D&#233;cio Mion Jr</bold>
          </p>
        </fn>
      </p>
      <p>Hypertension Unit - Discipline of Nephrology of the University of S&#227;o Paulo School of Medicine, S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> Felypressin has been added to local anesthetic to increase the length of the anesthetic effect and reduce toxicity during dental procedures. However, the effect on blood pressure remains uncertain, and this may be highly relevant in the dental treatment of hypertensive patients.</p>
      <p><bold>OBJECTIVE:</bold> To investigate the effect of felypressin on blood pressure in hypertensive patients with controlled BP.</p>
      <p><bold>METHODS:</bold> 71 subjects with these characteristics and in need of periodontal treatment were studied. After 10 minutes of rest, local anesthesia (prilocaine) was infiltrated with and without addition of felypressin. Then, a deep subgingival scaling was performed. Blood pressure was measured by an automated oscillometric device (DIXTAL DX2010). Ten minutes after the administration of the anesthetic, peak anesthetic action was recorded. The State-Trait Anxiety Inventory (STAI) was used to assess the patients' trait anxiety.</p>
      <p><bold>RESULTS:</bold> Systolic blood pressure increased after anesthesia, regardless of association with felypressin, throughout the dental procedure (p&lt;0.05) and this response can be explained, at least in part, by the trait anxiety levels of the subjects. However, a further increase in diastolic blood pressure was observed when prilocaine was associated with felypressin (p&lt;0.05), but this response did not change with trait anxiety levels.</p>
      <p><bold>CONCLUSION:</bold> Felypressin increased the diastolic blood pressure of hypertensive patients with controlled blood pressure. Patients with high trait anxiety presented increases in systolic blood pressure upon some procedures, suggesting that an increase in blood pressure might also be related to fear or anxiety.</p>
      <p><bold>Keywords:</bold> Felypressin; blood pressure; anesthesia, local; hypertension; periodontal diseases.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Felypressin is a synthetic hormone of the posterior pituitary lobe characterized by vasoconstrictor properties that is widely used in dental procedures<sup>1</sup>. Its vasoconstrictor action seems to be mediated by V1 receptors of the blood vessel smooth muscle cells<sup>2</sup>. However, it is noteworthy that the V1 receptor-mediated vasoconstrictor action is dependent on territory, since vessels of skeletal muscles and skin are more sensitive than renal vessels<sup>2</sup>. Anyway, felypressin has been widely added to local anesthetic solutions to increase the duration of the anesthetic effect and reduce the risk of toxicity during dental procedures<sup>3</sup>. Since its benefits are undeniable, its use is recommended by the Therapeutic Council of Dentistry of the United States of America<sup>3</sup> in association with all local anesthetics, because the absence of a vasoconstrictor promotes fast absorption of the anesthetic and, consequently, low anesthetic effectiveness. </p>
      <p>In Brazil, where hypertension affects 22-41% of the adult population<sup>4</sup>, dental surgeons frequently have to provide dental care to hypertensive patients. However, despite the aforementioned benefits for dental procedures, it is not yet clear if felypressin in addition with prilocaine increases arterial blood pressure (BP), especially in subjects with special conditions, as is the case of hypertensive patients<sup>5,6</sup>. Is true that the level of the felypressin-related blood pressure increases might be low; nonetheless, some subgroups such as hypertensive subjects may benefit from efforts to reduce a further felypressin-related cardiovascular risk. Furthermore, that the choice of the local anesthetic seems to influence the hemodynamic response during dental procedures<sup>7,8</sup> and, therefore, in the absence of any interaction with adrenergic receptors, it has been suggested that felypressin presents a lower incidence of side effects on hemodynamic responses<sup>9</sup>. For all these reasons, it is important to investigate the effect of felypressin on BP in hypertensive patients.</p>
      <p>Another aspect to be considered is the individual response to stress during dental procedures. It is known that the response to a particular stressor stimulus is greater in hypertensive than in normotensive subjects<sup>10</sup>. Therefore, the possible pain caused by dental procedures without anesthesia or even in situations of ineffective anesthesia can produce stress for the patient, resulting in the release of endogenous catecholamine, which sometimes reaches higher levels than the aggregate amount contained in a tube of anesthesia<sup>1</sup>. Thus, dental procedures also might increase BP as a result of fear or anxiety<sup>11</sup>, in addition to a possible increase in BP due to the action of felypressin<sup>12</sup>, especially in hypertensive patients.</p>
      <p>We hypothesized that BP might increase in the presence of felypressin during dental procedures, and the aim of this study was to investigate the effect of anesthesia, associated or not with felypressin on the BP of drug-controlled hypertensive patients during periodontal treatment.</p>
      <p>
        <bold>Methods and Materials</bold>
      </p>
      <p>The present study was performed as an open-label, randomized, two-way, two-treatment, single-dose study, after two hours of fasting, and the treatments were separated by a wash-out period of 10 minutes between the interventions (prilocaine or prilocaine plus felypressin) to comply with the crossover method proposed. Each subject was assigned a unique identification number and during the entire study, all the procedures were carried out by the same researchers, with a standardized protocol. The procedures were performed in accordance with the guidelines of the Helsinki Declaration for human experimentation and approved by the Ethics Committee of the General Hospital of the University of Sao Paulo, Brazil. All volunteers signed an informed consent form prior to their participation. The experimental design is present in <xref ref-type="fig" rid="en_aop05912fig01-body2">Figure 1</xref>.</p>
      <p content-type="asset">
        <fig id="en_aop05912fig01-body2">
          <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf01-en.jpg"/></fig>
      </p>
      <p>
        <bold>Subjects</bold>
      </p>
      <p>Seventy-one hypertensive patients under antihypertensive treatment and with controlled BP as evaluated upon their last medical visit (systolic and diastolic BP lower than 140/90 mmHg, respectively) were investigated. The sample included patients of both genders in need of periodontal treatment. Patients who presented diabetes mellitus, renal, coronary, heart or liver failure, and pregnant women were excluded.</p>
      <p>
        <bold>Preliminary assessments</bold>
      </p>
      <p>All patients underwent an initial dental examination. At arrival at the dentist's office, they were placed to rest, seated in a comfortable dentist's chair with the back at an angle of 45&#186; for 10 minutes. After this, their trait anxiety level was assessed and they were classified as patients with low or with high anxiety level. Subsequently, the dentist performed the assessment of oral health and verified the presence of periodontal disease. For this purpose, periodontal disease was diagnosed according to the periodontal index criteria (Periodontal Screening &amp; Recording - PSR). Briefly, this index identifies the presence of gingival inflammation and of aggravating local factors such as plaque and tartar attacking the gingival and periodontal tissue<sup>13</sup>. Patients who did not fulfill these criteria were excluded. Then, to familiarize them with the procedures, all patients were submitted to subgingival scaling without anesthetic procedures, since subgingival scaling is not painful. </p>
      <p>
        <bold>Anxiety assessment</bold>
      </p>
      <p>The State-Trait inventory (STAI)14 was used to assess the patients' anxiety level. This inventory is composed of two parts, with 20 statements each, and determines how the person usually feels in his/her life based on a scale, with a score range from 20 to 80. Thus the patients were classified according to their score as presenting "low anxiety" (score below or equal to 25) or "high anxiety" (score above 25).</p>
      <p>
        <bold>Blood pressure</bold>
      </p>
      <p>During the experimental session, BP was measured in a triplicate way and the mean was calculate for each period (rest, local anesthetic, subgingival scaling and anesthetic peak) with an automated oscillometric device (DIXTAL - model DX 2010, S&#227;o Paulo, Brazil) that is the result of the perfecting of DIXTAL - model DX 2710<sup>14</sup>, validated according to the international regulations<sup>15</sup>. The cuff used was the adequate size for the circumference of the patient's dominant arm: a) "adult" cuff with a 13 x 24cm inflatable bag for patients with arm circumference of 24 x 32cm; and, b) "obese" cuff with a 17 x 32cm inflatable bag for patients with arm circumference of 32 x 42cm. During the measurement, the cuff was positioned on the arm and adjusted for the height of the left ventricle<sup>16</sup>. </p>
      <p>
        <bold>Periodontal treatment</bold>
      </p>
      <p>During the periodontal treatment, all patients were instructed to take their antihypertensive drugs at 8:00 am, to ensure the antihypertensive action at the same time of the experimental session. The patients arrived at the dental office at 2:00 pm, after a postprandial period of 2 hours, in order to prevent any effect of food on BP.</p>
      <p>During the pre-intervention period, defined as REST, the patients were seated in a comfortable dentist's chair with the back at an angle of 45&#186; for 10 minutes, during which their BP was measured every two minutes. Then, the local anesthetic (prilocaine), with or without felypressin, was infiltrated using a syringe with a 30G carpule needle. This procedure was named as LOCAL ANESTHETIC period and lasted four minutes. The quantities used were 144mg 4% prilocaine without felypressin (2 tubes) and 108mg prilocaine with 0.11 UI of felypressin (2 tubes), totaling four tubes. It is noteworthy that the difference in the amount of prilocaine is due to commercial availability of local anesthetic, in which is only found prilocaine 3% with felypressin 0.03 IU, and prilocaine 4% without vasoconstrictor. During this step, BP was measured twice. After the anesthesia, the technical procedure for deep subgingival scaling was performed and BP was again measured every two minutes. This dental procedure, defined as SUBGINGIVAL SCALING period, is always painful and justifies the use of an anesthetic. The anesthetic peak of prilocaine or prilocaine associated with felypressin was reached 10 minutes after the anesthetic injection, and BP was measured twice. This period was defined as ANESTHETIC PEAK period. The instruments used during the deep subgingival scaling were McCall and Grayce curettes, sickles of the type scraped, and periodontal probes.</p>
      <p>
        <bold>Anesthetic simulation</bold>
      </p>
      <p>A subsample of 34 patients was invited to engage in an anesthetic simulation session one week before the experimental session, in which an anesthetic simulation with an empty syringe and needle was performed, in order to evaluate the effect of the procedure on BP. The details of the anesthetic simulation session were as described: rest, evaluation of oral health, and subgingival scaling in the preliminary assessments. This procedure was performed one week before the experimental session, immediately after the dental evaluation to assess the need for dental treatment.</p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>Considering a power of 80% and an alpha error of 5%, the minimal sample size necessary to detect a difference of 10 mmHg in BP was calculated to be 37 subjects.</p>
      <p>Data normality was checked by means of the Shapiro-Wilks test, using the statistical package SPSS for Windows (Statistical Package for Social Sciences, version 13.0, Chicago, IL, USA).</p>
      <p>The effects of prilocaine associated or not with felypressin were compared by a two-way ANOVA test for repeated measures, establishing anesthetic (prilocaine or prilocaine + felypressin) and stage (rest, anesthetic, subgingival scaling and anesthetic peak) as the main factors. Post-hoc comparisons were made using the Newman-Keuls test. Values of p&lt;0.05 were considered statistically significant, and data are presented as means and standard error. The software package used for these analyses was STATISTICA (Statistic for Windows 4.3, StatSoft Inc, Tulsa, OK, USA, 1993).</p>
      <p>The primary outcomes were changes in office BP during painful dentistry procedures and the effects of prilocaine associated or not with felypressin.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>Seventy-one hypertensive patients (44 women and 27 men) with BP controlled by antihypertensive treatment and in need of periodontal treatment completed the study. The characterization of the sample is presented in <xref ref-type="table" rid="tab1-body2">Table 1</xref>. It is noteworthy that the trait anxiety was measured in 36 patients only, because the other volunteers did not fulfill the forms completely.</p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gt01-en.jpg"/></table-wrap>
      <p>The effects of the anesthetic simulation session are presented in <xref ref-type="fig" rid="en_aop05912fig02-body2">Figure 2</xref>.</p>
      <p content-type="asset">
        <fig id="en_aop05912fig02-body2">
          <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf02-en.jpg"/></fig>
      </p>
      <p>During the anesthetic simulation session, both systolic and diastolic BP increased significantly (p&lt;0.05) compared to the other steps of the session (rest, assessment of oral health, and subgingival scaling).</p>
      <p><xref ref-type="fig" rid="en_aop05912fig03-body2">Figure 3</xref> shows the effect of anesthetic added or not with felypressin on BP. Regarding systolic BP, a significant effect of the stage factor was identified, since prilocaine, associated or not with felypressin, increased the systolic BP throughout the period of the dental visit (p&lt;0.05). However, regarding the diastolic BP, a significant interaction between the main factors (condition and stage) was found. Thus, diastolic BP increased during all dental procedures under both conditions, but this increase was greater when the anesthetic was associated with felypressin (p&lt;0.05).</p>
      <p content-type="asset">
        <fig id="en_aop05912fig03-body2">
          <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf03-en.jpg"/></fig>
      </p>
      <p>In a complementary analysis, subjects with low (score <underline>&lt;</underline> 25) and high (score &gt;25) trait anxiety were compared, and it was observed that the systolic BP increased significantly during anesthesia and subgingival scaling only in the patients with highest trait anxiety (<xref ref-type="fig" rid="en_aop05912fig04-body2">Figure 4</xref>). However, no significant difference was observed in diastolic BP (p&gt;0.05). </p>
      <p content-type="asset">
        <fig id="en_aop05912fig04-body2">
          <graphic xlink:href="1678-4170-abc-99-02-0724-00062-gf04-en.jpg"/></fig>
      </p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The originality of the present study is the finding that anesthetic associated with felypressin increases the diastolic BP of hypertensive patients with medication-controlled BP. </p>
      <p>We found here that acute infusion of prilocaine assoc iated with felypressin promotes an increase in diastolic but not in systolic BP. Our study is in agreement with that of Inagawa et al<sup>17</sup>, who found that, in male Japanese white tracheotomized rabbits, the diastolic BP increased significantly, without change in systolic BP. However, our study differs from others with human experimentation that showed that felypressin is not associated with BP increases<sup>18</sup>. This difference can be justified by the fact that we investigated hypertensive patients with controlled BP, and the effect of felypressin might be different in hypertensive patients with uncontrolled BP, because the presence of an already elevated BP may cover up the BP response to felypressin. Furthermore, it is noteworthy that V1 receptors can trigger a powerful vasoconstrictor response<sup>19</sup> and might therefore contribute to the tonic control of circulation, because specific antagonists of V1 receptors produce a slight, but long-lasting fall in BP2. However, the effect of felypressin on the vascular tone is still a controversial issue.</p>
      <p>The use of a local anesthetic, whether associated or not with a vasoconstrictor, in the dental care of hypertensive patients and its adverse effects on BP were evaluated by several authors<sup>3,16,20</sup>, but there are no conclusive studies on this topic up to far. In the present study, we identified a BP elevation during all procedures, and a partial analysis of the data showed that this elevation tended to be more pronounced during the anesthetic procedure. Thus, two hypotheses arise: a) prilocaine also increases BP; and b) dentistry procedures are stressful enough to increase BP, regardless of prilocaine. Based on this initial analysis, we decided to include an anesthetic simulation procedure with an empty syringe and needle, to monitor the BP at the time of anesthesia. During this simulation, there was a significant elevation in systolic BP, suggesting that fear and anxiety can trigger such a response. In fact, Gortzack et al<sup>17</sup> also demonstrated a more pronounced BP elevation during the administration of a local anesthetic, followed by reduction after removal of the needle.</p>
      <p>It has been suggested that beta-blockers might reduce the release of endogenous adrenaline<sup>16</sup> and, therefore, interfere with the BP response. Coincidentally, in our study, 58% of the subjects were under beta-blocker treatment and 58% of the subpopulation in which the level of stress was assessed showed mild anxiety. It is therefore possible to think that the use of beta-blockers might affect the BP responses to stress. Thus, we decided to evaluate our patients separately according to their use or not of beta-blockers (data not shown). However, no significant difference was found for either systolic or diastolic BP during the entire experimental protocol (p&gt;0.05).</p>
      <p>It is known that the response to a particular stressor stimulus is greater in hypertensive than in normotensive subjects. Furthermore, it is noteworthy that among hypertensive patients there is variability in stress index. In a subsample of our study, 42% of the subjects were classified as high anxiety subjects and prilocaine without vasoconstrictor was found to promote a systolic BP increase (<xref ref-type="fig" rid="en_aop05912fig04-body2">Figure 4</xref>); yet, when associated to felypressin, this response was not observed (p&gt;0.05), suggesting that blood pressure response to felypressin is not influenced by the anxiety level.</p>
      <p>
        <bold>Conclusions</bold>
      </p>
      <p>In conclusion, the present findings indicate that felypressin increases the diastolic BP, regardless of its anesthetic properties. Furthermore, a significant increase in systolic BP occurs in hypertensive patients whose BP is controlled by antihypertensive treatment. Patients with high trait anxiety presented systolic BP increases upon some procedures, suggesting that an increase in BP might also be related to fear or anxiety. Finally, this study contributed to unraveling the hemodynamic risk that hypertension can present with prilocaine + felypressin use. However, it not belies the dentistry practice that is widely used in the clinic routine for this population.</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 article is part of the thesis of master of Ana L&#250;cia Aparecida Bronzo from the Faculdade de Medicina da Universidade de S&#227;o Paulo (Disciplina de Nefrologia ministrada pelo Professor D&#233;cio Mion Junior).</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
