Paula Abdo - R3 UTI Pediátrica no HRAS/HMIB/SES/DF Coordenação: Nathalia Bardal www.paulomargotto.com.br Brasília, 14 de outubro de 2014 Canal arterial.

Apresentação em tema: "Paula Abdo - R3 UTI Pediátrica no HRAS/HMIB/SES/DF Coordenação: Nathalia Bardal www.paulomargotto.com.br Brasília, 14 de outubro de 2014 Canal arterial."— Transcrição da apresentação:

1 Paula Abdo - R3 UTI Pediátrica no HRAS/HMIB/SES/DF Coordenação: Nathalia Bardal www.paulomargotto.com.br Brasília, 14 de outubro de 2014 Canal arterial patente nos pré-termos: temos as respostas corretas? BioMed Research International Volume 2013, Article ID 676192,15pages – Publicação online MUDA BRASIL!

2 INTRODUÇÃO  Incidência da persistência do (RN) pré-termo (RNPT) varia entre 40-60% no terceiro dia de vida  Não há consenso quanto ao tratamento da PCA  Achar respostas:  Tratar ou não tratar?  Quando tratar?  Como tratar?

3 TRATAR OU NÃO TRATAR?  PCA: há um grande debate se deve tratar ou não devido:  Condição patológica que causa morbidade e mortalidade  Condição fisiológica

4 EVIDÊNCIAS PARA TRATAR ASSOCIAÇÃO ENTRE PCA E MORBIDADE/MORTALIDADE NOS RNPT  Presença de shunt E-D aumenta fluxo e pressão pulmonar  RNPT já possuem pressão oncótica mais baixa, permeabilidade capilar aumentada: edema alveolar e intersticial e reduz complacência pulmonar  Parâmetros ventilatórios mais altos, maior tempo de ventilação mecânica, maior chance de displasia broncopulmonar

5 EVIDÊNCIAS PARA TRATAR ASSOCIAÇÃO ENTRE PCA E MORBIDADE/MORTALIDADE NOS RNPT  Fator de risco para: injúria renal, hemorragia intraventricular, leucomalácia periventricular, enterocolite necrosante (ECN).  A evidência dessas associações é conflituosa. Não se sabe se são resultado do shunt E-D, do tratamento do canal ou da própria prematuridade.

6 EVIDÊNCIAS PARA TRATAR ASSOCIAÇÃO ENTRE PCA e Hemorragia intraventricular em RNPT 1. Fator de risco para hemorragia intraventricular: a ultrassonografia cerebral demonstrou redução no fluxo sanguíneo cerebral / Disfunção miocárdica: sobrecarga a Esquerda gerando piora da perfusão sistêmica  Fator de risco para a ECN: fluxo reduzido na aorta abdominal e mesentérica superior

7 EVIDÊNCIAS PARA TRATAR ATRASO NO INÍCIO DO TTO FARMACOLÓGICO ESTÁ ASSOCIADO A MENOR RESPOSTA AO INIBIDORES DA COX  Em RNPT, o tecido do canal se desenvolve e se torna menos regulado pela prostaglandina com o passar do tempo  O atraso no início da terapia, gera menor resposta ao tratamento e consequente menor taxa de sucesso e aumento da taxa de tratamento cirúrgico

8 EVIDÊNCIAS PARA TRATAR TOLERAR PCA PODE AUMENTAR O RISCO PARA DISPLASIA BRONCOPULMONAR:  Estudo Holandês, com 129 RNPT, PN 500-1500g demonstrou maior taxa de displasia broncopulmonar e taxa combinada de morte após o dia 7.  Índices de displasia broncopulmonar e morte foram maiores no período de tolerância permissiva dos canais (restrição hídrica ou indometacina/cirurgia nos canais grandes com necessidade de suporte ventilatório) em relação aos tratamentos instituídos mais precocemente

9 EVIDÊNCIAS PARA NÃO TRATAR ALTO ÍNDICE DE FECHAMENTO ESPONTÂNEO  Ocorre em quase 50% dos recém-nascidos a termo (RNT) em 24h. Em 90% em 48h. E em todos, com 72h.  Em RNPT > 30sem o fechamento ocorre por volta do 4 0 dia de vida  Estudo prospectivo mostrou fechamento nos primeiros 10 dias de vida em 35% dos muito baixo peso e 70% em > 28 sem

10 EVIDÊNCIAS PARA NÃO TRATAR AUSÊNCIA DE EFICÁCIA DO TRATAMENTO  estudos falharam em demonstrar uma vantagem a longo prazo em se tratar a PCA  Não demonstraram menores taxas de displasia broncopulmonar, enterocolite necrosante e deficiente neurodesenvolvimento ou morte

11 EVIDÊNCIAS PARA NÃO TRATAR EFEITOS COLATERAIS DO TRATAMENTO FARMACOLÓGICO  Muitos efeitos sistêmicos devido vasoconstrição não seletiva  Indometacina reduz muito fluxo sanguíneo renal, mesentérico, cerebral e coronariano

12 EVIDÊNCIAS PARA NÃO TRATAR EFEITOS COLATERAIS DO TRATAMENTO CIRÚRGICO  Fechamento precoce demonstrou ser um fator de risco indepentente para desenvolvimento de displasia broncopulmonar e impede crescimento pulmonar  Estudos mostraram também um risco maior de desenvolver retinopatia da prematuridade e alteração no desenvolvimento neurológico em comparação com tratamento farmacológico

13 EVIDÊNCIAS PARA NÃO TRATAR ACHADOS ECOCARDIOGRÁFICOS. Há vários critérios ecocardiográficos para a definição de PCA hemodinamicamente significativa, embora não constituam critérios que definem a necessidade de tratamento:  Diâmetro da PCA> 1,4mm  Relação AE/aorta > 1,4  Relação entre diâmetro do canal e superfície corporal  Diástole reversa na artérias: aorta, mesentérica, cerebral e renal

14 EVIDÊNCIAS PARA NÃO TRATAR 1. MARCADORES BIOQUÍMICOS  BNP (B-type natriuretic peptide ): quando alto, tem um valor preditivo de baixa resposta a indometacina e necessidade de tratamento cirúrgico  TROPONINA: aumenta na presença de canal com repercussão hemodinâmica  No entanto, estudo recente de Hammerman et al (Pediatric Cardiology,vol.31,no.1,pp.62–65, 2010) não mostrou diferenças nas concentrações destes dois biomarcadores nos que responderam ou não ao tratamento e que a diminuição dos níveis destes marcadores não se correlacionou a a falha ou suscesso no tratamento

15 QUANDO TRATAR?

16  Intervenção precoce para canais assintomáticos possuem maiores índices de sucesso, mas tem maior risco de exposição desnecessária  Intervenção tardia apenas em canais sintomáticos diminui a exposição desnecessária, porém aumenta chance de falha no tratamento e necessidade de ligadura cirúrgica

17 QUANDO TRATAR?  3 ESTRATÉGIAS 1. Tratamento profilático : logo após o nascimento, sem dados sobre estágio da PCA 2. Tratamento pré- sintomas 3. Tratamento nos sintomáticos quando há repercussão hemodinâmica

18 QUANDO TRATAR?  TRATAMENTO PROFILÁTICO: Iniciar nos primeiros dias de vida (de preferência nas primeiras 24h de vida)  Em RNPT a resistência vascular pulmonar/ artéria pulmonar reduz após as primeiras 24h de vida. Com isso aparecerão os sintomas de PCA com 48-72h de vida

19 QUANDO TRATAR? Critérios de inclusão: IG e peso  < 32sem / < 1500g  Mahony et al. estudaram o efeito da indometacina profilática em menores de 1700g: maior benefício nos menores de 1000g (>1000g maior chance de fechamento espontâneo)

20 QUANDO TRATAR?  TRATAMENTO PROFILÁTICO  Reduz a incidência de PCA sintomáticas  Reduz hemorragia intraventricular  Estudos mais recentes não demonstraram benefícios na taxa de sobrevivência ou deficiências a longo termo  Tanto o uso profilático de indometacina como ibuprofeno tem sido abandonados

21 QUANDO TRATAR?  PRÉ-SINTOMAS  Objetivo é restringir o uso para RN com PCA, ainda assintomáticos, ao invés de tratar todos de forma profilática  Reduz exposição desnecessária e consequentemente reduz a possibilidade de efeitos adversos

22 QUANDO TRATAR?  PRÉ-SINTOMAS  3 metanálises demonstraram que o tratamento reduziu a incidência de PCA sintomática e duração da oxigenoterapia  Sem efeito sobre a mortalidade, displasia broncopulmonar, hemorragia intraventricular, retinopatia da prematuridade, duração da ventilação

23 QUANDO TRATAR?  TRATAMENTO SINTOMÁTICO  Aguardar sinais de repercussão hemodinâmica possibilita o fechamento espontâneo  A dificuldade é determinar quando um canal é hemodinamicamente importante  Gersony et al. compararam tratamento conservador x indometacina x cirurgia e evidenciaram aumento significativo no fechamento dos PCA com indometacina + tratamento conservador

24 QUANDO TRATAR?  TRATAMENTO SINTOMÁTICO parece ser a forma mais sensata de tratamento  São necessários mais estudos comparando tratamento sintomático x tratamento conservador

25 COMO TRATAR?

26 1. Tratamento conservador 2. Tratamento farmacológico 3. Tratamento cirúrgico

27 COMO TRATAR?  TRATAMENTO CONSERVADOR  Restrição hídrica: reduz o volume circulante e a sobrecarga na circulação pulmonar, melhorando a função respiratória  Reduz débito cardíaco que gera redução do fluxo sanguíneo sistêmico  Estudo prospectivo com 18 RN de baixo peso, com canal com repercussão, restringiram taxa hídrica (100- 120). Não alterou gasometria, necessidade de O2, diâmetro da PCA ou pressão arterial

28  TRATAMENTO CONSERVADOR  Uso da furosemida é contraditório  Aumenta produção de prostanglandinas, podendo reduzir a resposta do canal à indometacina  Fluxos de O2 mais baixos: estudo retrospectivo com 263 RNPT extremo baixo peso tiveram maior incidência de canais com repercussão, porém menor necessidade de tratamento cirúrgico

29 COMO TRATAR?  TRATAMENTO FARMACOLÓGICO  Indometacina: Profilático: 0,1mg/kg/dia // terapêutico 0,2mg/kg/dose 12/12h -Taxa fechamento depende do peso de nascimento -1000-1750g: 80-86% // < 1000g: 54% -Em caso de falha, um segundo ciclo foi eficaz em 44%

30 COMO TRATAR?  TRATAMENTO FARMACOLÓGICO  Indometacina: Uma metanálise comparou ciclos longos (+ de 4 doses) com ciclos curtos: não houve diferença entre o fechamento do canal, necessidade de cirurgia, mortalidade, displasia broncopulmonar ou hemorragia intraventricular Ciclos longos tiveram maior taxa de enterocolite necrosante e injúria renal

31 COMO TRATAR?  TRATAMENTO FARMACOLÓGICO  Indometacina: Efeitos adversos: hiponatremia, oligúria, sangramento, injúria renal. Porém são transitórios Devido vasoconstrição não seletiva Contra-indicação da indometacina: infecção grave presumida ou comprovada, sangramento ativo, trombocitopenia, coagulopatia, alteração significativa da função renal, enterocolite necrosante, cardiopatia canal dependente

32 COMO TRATAR?  IBUPROFENO  Não reduz fluxo renal, cerebral ou intestinal  Dose de ataque: 10mg/kg ; seguido de 5mg/kg/d por 2 dias  Erdeve et al. compararam VO x IV: oral teve uma taxa inicial maior de fechamento do canal e menor incidência de displasia broncopulmonar. Porém houve uma taxa maior de reabertura do canal.

33 COMO TRATAR  IBUPROFENO  Inibe adesão plaquetária  Desloca a bilirrubina da albumina e aumenta bilirrubina livre circulante  Contra-indicações: falência renal, hiperbilirrubinemia, plaquetopenia severa, perfuração gastrointestinal, enterocolite necrosante, cardiopatia canal dependente

34 COMO TRATAR  IBUPROFENO (1) x INDOMETACINA (2)  Eficácia semelhante no fechamento  (1) Menos nefrotóxico e menos efeito de vasoconstrição sistêmica  Sem diferença na mortalidade, displasia broncopulmonar, hemorragia intraventricular

35 COMO TRATAR?  PARACETAMOL  Nova opção devido maior segurança e baixo preço  15mg/kg/dose 6/6h por 3 dias  Relatadas altas taxas de sucesso (71-100%)  Paracetamol EV pode aumentar nível das transaminases ?  Dose menor já seria eficaz?  Necessidade de mais estudos

36 COMO TRATAR  CIRURGIA  Duas formas: ligadura ou clip vascular  Duas formas: cirurgia precoce para todos após falha do tratamento farmacológico ou cirurgia tardia apenas quando houver comprometimento cardiopulmonar  Complicações a curto prazo: paralisia unilateral da corda vocal, paresia diafragmática, eventração diafragmática, sangramento, quilotorax

37 COMO TRATAR  CIRURGIA  Vários estudos retrospectivos demonstraram ausência de benefício pulmonar e maior risco de displasia broncopulmonar  Outros estudos retrospectivos demonstraram maior taxa de alteração neurosensorial, atraso no desenvolvimento cognitivo aos 18 meses

38 CONCLUSÃO  O tratamento deve ser individualizado de acordo com a clínica, ecocardio e marcadores que indiquem repercussão hemodinâmica  Restrição hídrica não possui benefício pulmonar ou sistêmico nesses pacientes  Ibuprofeno e indometacina são igualmente eficazes

39 CONCLUSÃO  Cirurgia parece aumentar o risco para um deficiente neurodesenvolvimento, displasia broncopulmonar e retinopatia da prematuridade.  Parece mais adequado reservar a cirurgia para os RN com falha do tratamento farmacológico + evidência ecocardiográfica de PCA grande ou necessidade de parâmetros/FiO2 altos

40 Consultem o artigo integral!  ABDEL-HADY, H.; NASEF, N.; SHABAAN, A. E.; NOUR, I. Patend ductus arteriosus in preterm infants: do we have the right answers?. Neonatal Intensive Care Unit, Egito, outubro 2013.  Patent ductus arteriosus in preterm infants: do we have the right answers? Patent ductus arteriosus in preterm infants: do we have the right answers?  Abdel-Hady H, Nasef N, Shabaan AE, Nour I.  Biomed Res Int. 2013;2013:676192. Artigo Integral! Clicar Aqui!

41  Abstract  Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.

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56 Nota do Editor do site, Dr. Paulo R. Margotto Consultem também!Aqui e Agora! “eu fui inundado com tantas dúvidas e tantos erros e aparentemente o único benefício que tive através da educação e instrução, é que cada vez mais eu continuo a descobrir a minha própria ignorância” Augusto Sola

57 Objetivo deste estudo  para determinar se a) os índices ecocardiográficos de deficiente performance miocárdica estiveram associados com o desenvolvimento subsequente de hipotensão arterial após a ligação cirúrgica do canal arterial b) a presença de baixa concentrações de cortisol pós- operatórias foram associados com índices de performance miocárdica prejudicados (ecocardiograma)  Com os resultados obtidos, os autores especulam que baixas concentrações de cortisol no pós-operatório pode levar a menor regulação dos receptores adrenérgicos, que por sua vez pode contribuir para falha da resposta à catecolamina na manutenção do tônus vascular e pressão arterial. Hipotensão catecolamina resistente e performance card í aca ap ó s liga ç ão do canal arterial p é rvio Autor(es): Noori S et al. Apresenta ç ão: Helena Recart Costa, Raissa Rezende, Paulo R. Margotto, M á rcia Pimentel de Castro

58 Morbimortalidade nos rec é m-nascidos pr é -termos com persistência do canal arterial no dia 3 Autor(es): Anna Sellmer, Jesper Vandborg Bjerre, Michael Rahbek Schmidt et al. Apresenta ç ão: Cl á udio Rodrigues J ú nior,Danilo Lima Souza, Paulo Heitor Godoi, Fernando S. Goulart, Paulo R. Margotto O que já se sabe sobre este tema ▸ A freqüência da persistência do canal arterial (PCA) é inversamente proporcional à idade gestacional. ▸ A relevância clínica da PCA em neonatos prematuros é questionável. ▸ O resultado de uma PCA está associada com a magnitude shunt através da PCA e a capacidade do recém-nascido para lidar com ela. O que este estudo acrescenta ▸ A presença de uma PCA no 3º dia de vida é associada ao aumento da mortalidade e severa morbidade em recém-nascidos <28 semanas de gestação. ▸ Em recém-nascidos < 28 semanas de gestação uma PCA com diâmetro ≥ 1,5 milímetros no 3º dia de vida está associada com maiores chances de hemorragia intraventricular, displasia broncopulmonar e mortalidade ou morbidade grave.

59  Existem algumas limitações deste estudo. O diâmetro da PCA está sujeito a erros de medição e variabilidade inter-observadores.  No entanto: estratificação por idade gestacional acabou por ser um modificador maior da associação entre PCA e morbimortalidade. Para otimizar poder os autores introduziram um resultado combinado de morbidade grave e morte.

60  o estudo recente de Oncel et al compararam o paracetamol oral com o ibuprofeno oral e não houve diferença entre os grupos quanto às taxas de fechamento, de retratamento e de reabertura do canal arterial, assim como funções renais e hepáticas. Qual seria o mecanismo de ação? A Prostaglandin syntetase tem componentes ciclooxigenase (COX) e peroxidase (POX) que operam em sítios ativos distintos com diferentes atividades catalíticas;a ciclooxigenase cataliza o começo da síntese de prostanóide a partir do ácido aracdônico; o ibuprofeno e indometacina competem com o ácido aracdônico pelos sítios ativos da cicloxigenase; já o paracetamol parece atuar no segmento da peroxidase, reduzindo a concentração local de peróxido. Acreditamos que o paracetamol possa vir a constituir uma opção terapêutica em situações em que DEVEMOS fechar o canal arterial (presença de hemorragia pulmonar, pressão arterial de difícil controle, altos parâmetros no ventilador), mas situações nos impossibilitam de usar o ibuprofeno oral (medicação que habitualmente usamos) como má digestibilidade, além de presença de trombocitopenia (<1000.000/mm3), enterocolite necrosante, insuficiência renal, hemorragia intraventricular, hiperbilirrubinemia. Paracetamol oral versus ibuprofeno oral no manuseio do ductus arteriosus em rec é m-nascidos pr é -termos: ensaio controlado randomizado Autor(es): Oncel MY, Yurttutan S, Endeve O et al. Apresenta ç ão: Camila Rodrigues, Isabela Lobo, Karine Frausino, M á rcia Pimentel de Castro, Paulo R. Margotto

61  Os neonatologistas tem a obrigação ética de conduta adequada com critérios objetivos para a terapia de fechamento da PCA  Devemos lembrar sempre: Na UTI, identificar subgrupos de neonatos com maior risco para resultados adversos (e nestes, somente nestes atuar!) Persistência do canal arterial:quando tratar? Fatos e Mitos (VI Curso de Neonatologia, 28/O1/2014, Fortaleza, CE) Autor(es): Paulo R. Margotto

62  Seria uma abordagem simplista demais dizer que devemos tratar todos os PCA ou nenhum. Precisamos entender os efeitos fisiológicos da PCA em cada criança. Temos que nos adaptar aos bebês e não tratá-los como se todos fossem iguais. Para este objetivo, temos que ser capazes de classificar os efeitos que irão permitir a identificar os canais arteriais pérvios através da ecocardiografia ou desenvolver tratamentos específicos que nos proporcionem os melhores benefícios sem causar dano às crianças. Este é mais um motivo para aprender a usar o US: para que possamos avaliar a relevância da PCA para tomarmos uma decisão mais bem informada se devemos tratar ou não os nossos pacientes. Mais estudos são necessários, principalmente na área farmacocinética e farmacodinâmica dos tratamentos que hoje dispomos. Canal arterial patente:da fisiologia ao tratamento Autor(es): Martin Kluckow (Austr á lia). Realizado por Paulo R. Margotto Concluindo, o raciocínio lógico para nós seria primeiramente identificar um grupo de crianças que tem PCA grande que mais se beneficiarão com o tratamento. Então parece ser a direção a ser seguida: tentativa de identificar este grupo de bebês que terão benefícios e não expor este outro grupo a efeitos colaterais

63 OBRIGADA! Drs. Joaquim Bezerra, Paulo R. Margotto e Paula Abdo