BRAZILIAN JOURNAL OF ANESTHESIOLOGYOffi cial Publication of the Brazilian Society of Anesthesiology

Volume 64, Número 1, Janeiro – Fevereiro, 2014 Disponível on-line em Espanhol

REVISTABRASILEIRA DEANESTESIOLOGIA

Volume 64Número 1Janeiro – Fevereiro, 2014

ISSN 0104- 0014

ÓRGÃO OFICIAL DA SOCIEDADE BRASILEIRA DE ANESTESIOLOGIAR

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Disponível on-line em Espanhol

Impact Factor 2012: 0.428 © Thomson Reuters Journal Citation Reports,

Science Edition (2012)

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REVISTA BRASILEIRA DE ANESTESIOLOGIA

Editor-Chefe/Editor-in-ChiefMário José da Conceição

Coeditor/Co-editorMaria Angela Tardelli

Editores associados/Associate EditorsJosé Reinaldo Cerqueira BrazLuiz Marciano CangianiJudymara Lauzi Gozzani

Conselho editorial/Editorial BoardAna Maria CaetanoAntônio Leite Oliva FilhoAntônio Márcio S. Arantes PereiraAntônio Roberto CarrarettoDavid FerezDurval Campos KraycheteEdno MagalhãesGetúlio Rodrigues de Oliveira FilhoIrimar de Paula PossoIsmar Lima CavalcantiFlorentino F. MendesGuilherme Antonio Moreira Barros

João Batista Santos GarciaJosé Otávio Costa Auler JúniorJosé Roberto NocitiLigia Andrade da Silva Telles MathiasLuiz Antônio VaneMarcelo Luís Abramides TorresMarcos Guilherme Cunha CruvinelMaria José Carvalho CarmonaMarildo A. GouveiaMiriam Seligman MenezesNilton Bezerra do ValeOnofre Alves NetoOscar PiresPedro Paulo TanakaRogean Rodrigues NunesSergio D. BelzarenaYara Marcondes Machado Castiglia

Consultores estrangeirosAlexandru GottliebPeter S. A. GlassRajinder K. Mirakhur

A Revista Brasileira de Anestesiologia aceita para publicação trabalhos de colaboradores nacionais ou estrangeiros. Os artigos são publi-cados em língua portuguesa e inglesa, com resumo em espanhol.Os artigos devem ser enviados pela Internet seguindo as instruções disponíveis no Portal da SBA (www.sba.com.br), página da RBA pelo link Artigos para Publicação ou pelo endereço http://ees.elsevier.com/bjan.Os artigos submetidos à apreciação do Conselho Editorial devem obedecer às Normas aos Autores contidas no verso desta página.Os originais enviados à Revista Brasileira de Aneste siologia serão publicados a critério do Editor e do Conselho Editorial e tornam-se pro priedade da Sociedade Brasileira de Anes te siologia. Sua reprodução no todo ou em parte poderá ser feita com prévia autorização.As citações da Revista Brasileira de Aneste sio logia devem ser abreviadas para Rev Bras Anes tesiol.A Revista Brasileira de Anestesiologia não assume qualquer responsabilidade pelas opiniões emitidas nos trabalhos assinados.

The Revista Brasileira de Anestesiologia accepts for publication papers from brazilian and foreign authors. Articles are published in Portuguese and English with Spanish sum maries.The articles must be sent through the Internet following the instructions presented at SBA Portal (www.sba.com.br), at the RBA site, accessing the link Articles for Publication, or through the address http://ees.elsevier.com/bjan.Articles submitted to the Editorial Board´s appreciation shall comply with the Authors´ Guides on the back of this page.Original articles submitted to the Revista Brasileira de Anestesiologia will be published on the sole Editor and Editorial Board’s discretion and willbecome property of the Brazilian Society of Anesthesiology. Articles or parts of them may be reproduced only with previous autho rization.Revista Brasileira de Anestesiologia quo tations shall be abbreviated to Rev Bras Anestesiol.The Revista Brasileira de Anestesiologia takes no responsability for the opinions stated in signed articles.

Editada por/Edited bySOCIEDADE BRASILEIRA DE ANESTESIOLOGIARua Prof. Alfredo Gomes, 36, Rio de Janeiro, RJ, Brasil – 22251-080Tel: 21 3528-1050 – Fax: 21 3528-1099www.sba.com.brE-mail: sba@sba.com.br

Publicada por/Published byElsevier Editora Ltda.RJ: Tel: 21 3970-9300SP: Tel: 11 5105-8555www.elsevier.comISSN/$ - see metter © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Órgão ofi cial da

Departamento de Anestesiologia da Associação Médica Brasileira

NORMAS AOS AUTORES

Os artigos para publicacao deverao ser encaminhados com exclusividade para a Revista Brasileira de Anestesiologia pelo site http://ees.elsevier.com/bjan. Não serão aceitos ar-tigos já publicados em outros periódicos.

A Revista Brasileira de Anestesiologia classifica os artigos nas seguintes catego-rias:a) Artigos Científicos: Novas informações de pesquisa clínica ou experimental. b) Revisões: Artigos de síntese, de assuntos bem estabelecidos, com análise crítica

das referências bibliográficas consultadas e conclusões, revisões sistemáticas.c) Informações Clínicas: Relatos de casos clínicos, apresentação de novas técnicas,

métodos e equipamentos.d) Artigos Diversos: Aqueles que não se enquadram nas categorias acima, de interesse

para a Anestesiologia.e) Artigos Especiais: Revisões de assuntos de interesse da especialidade.f) Cartas ao Editor: Críticas à matéria publicada, de maneira construtiva, objetiva e

educativa. As discussões de assuntos específicos da Anestesiologia serão publicadas a critério do Editor.

g) Editoriais.Aprovação para Publicação: Todos os artigos propostos à publicação serão previamen-te submetidos à apreciação de dois ou mais membros do Conselho Editorial ou outros Consultores Especializados no assunto. Quando aceitos, estarão sujeitos a pequenas correções ou modificações que não alterem o estilo do autor. Eventuais modificações na forma, estilo ou interpretação só ocorrerão após prévia consulta. Quando recusa-dos, os artigos serão devolvidos com a justificativa do Editor-Chefe. OBS: Para aprovação final do artigo o autor e os co-autores deverão assinar Termo

de Cessão dos Direitos Autorais à Sociedade Brasileira de Anes tesiologia e à Elsevier Editora Ltda, cujo teor será enviado pelo Editor-Chefe.

Correção Final: Os artigos para publicação serão encaminhados ao autor para as cor-reções cabíveis e devolução no menor prazo possível. Se houver atraso na devolução da prova, o Editor-Chefe reserva-se o direito de publicar, independentemente da cor-reção final.

Será enviado ao autor cujo endereço eletrônico foi indicado para correspondência, ficando o mesmo responsável pela apreciação final da matéria, estando os demais de acordo com a publicação da mesma.

Formas de Apresentação dos Trabalhos: Título: O título do artigo deve ser curto, claro e conciso para facilitar sua classifica-ção. Quando necessário, pode ser usado um subtítulo. Autor(es): O(s) nome(s) completo(s) do(s) autor(es) e seus títulos e filiações à Socie-dade ou Instituições. Nomes de outros colaboradores podem ser citados no final, em agradecimentos. Indicar o local onde se realizou o estudo.Resumo Estruturado: Para artigos científicos destacar: Justificativa e Objetivos, Mé-todo, Resultados e Conclusões. Para informações clínicas destacar: Justificativa e Ob-jetivos, Relato do Caso e Conclusões. Para artigos de revisão destacar: Justificativa e Objetivos, Conteúdo e Conclusões.Para todos os artigos, indicar os Unitermos para a classificação bibliográfica, se-gundo Greene NM – Key Words in Anesthesiology, 3rd Ed, New York, Elsevier ou mais recente.Texto: Iniciar o texto, sem indicar o(s) autor(es) nem local onde foi realizado. Os artigos científicos devem apresentar os seguintes capítulos: Introdução, Método, Re-sultados, Discussão, Resumo e Referências. Referências: O artigo deve conter apenas as referências consultadas, numeradas conforme a entrada no texto. As outras citações de autores já enumerados deverão indicar exclusivamente o numeral de referência. Evitar a citação do nome do autor em destaque. Não se recomenda a citação de trabalho não publicado ou apresentado em Eventos Médicos. Referências com mais de cinco anos, de livros texto e resumo de congressos, devem limitar-se às que são fundamentais. Incluir referências acessíveis aos leitores. Quando a citação for de artigo já aceito para publicação, incluir “em processo de publicação”, indicando a revista e o ano. Comunicações pessoais não são aceitas. Utilize o seguinte modelo: Revistas: Nome(s) do(s) autor(es), inicial(is) do(s) pré-nome(s) – título do trabalho.

Título da revista (abreviado de acordo com o Index Medicus), ano da publicação; volume: número da primeira e última páginas.

Pereira E, Vieira ZEG – Visita pré-anestésica, responsabilidade intransferível do anestesiologista. Rev Bras Anestesiol, 1977;27:337-353.

Livros: Nome(s) do(s) Editor(es), inicial(is) do(s) pré-nome(s) – título do livro (ini-ciais com letra maiúscula), volume e edição, cidade onde o livro foi editado, Edito-ra, ano de publicação e número(s) da(s) página(s) da citação.

Rigatto M – Fisiopatologia da Circulação Pulmonar, 1ª Ed, São Paulo, Fundo Editorial Procienx, 1973;53-55.

Capítulos: Nome(s) do(s) autor(es), inicial(is) do(s) pré-nome(s) – título do capítulo. em: nome(s) do(s) editor(es), inicial(is) do(s) pré-nome(s) – Título do livro (iniciais com letra maiúscula), volume e edição, cidade onde foi editado, Editora, ano da publicação e página(s) da citação.

Coelho A – Anatomia do Sistema Específico de Condução, em: Germiniani H – Diag-nóstico e Terapêutica das Arritmias Cardíacas. São Paulo, Fundo Editorial Procienx, 1972;3-10.

Nota: Não se deve colocar pontuação nos nomes ou abreviaturas dos perió dicos citados. Quando houver menos de três autores, cite-os todos e quando houver mais de três, cite somente os três primeiros, seguidos de “et al.”.

Ilustrações: Enumerar ilustrações de acordo com a ordem de entrada no texto. Enu-merar figuras em algarismos arábicos. Enumerar quadros e tabelas em algarismos ro-manos. Indicar, no texto, o local preferencial de entrada de cada ilustração (Entra Figura x, por exemplo). Usar fotos em branco e preto. O mesmo resultado não deve ser

expresso por mais de uma ilustração.Uso de Recursos Digitais: Textos obrigatórios em formato DOC (Winword): Manuscript, Title Page (página com os dados completos do artigo e de seus autores), Cover Letter (carta de apresentação do artigo ao Editor), e Author Agreement (declaração de ine-ditismo e não submissão e/ou publicação duplicada); figuras em barras ou linhas XLS (padrão Excel); e fotos e figuras, com resolução mínima de 300 dpi, em formato JPG. Não inserir títulos e legendas nas ilustrações. Não inserir ilustrações no corpo do texto. Cada ilustração deve ter arquivo individual. O nome dos arquivos deve expressar o tipo e a numeração da ilustração (Figura 1, Tabela II, por exemplo). Títulos e legendas das ilustrações, devidamente numerados, devem estar no arquivo de texto. Cópias ou reproduções de outras publicações serão permitidas apenas mediante a anexação de autorização expressa da Editora ou do Autor do artigo de origem.Abreviaturas: As abreviaturas não são recomendáveis, exceto as reconhecidas pelo Sistema Internacional de Pesos e Medidas, ou aquelas consignadas e consagradas nas publicações médicas. Quando as abreviaturas forem em grande número e relevantes utilizar suas definições (Glossário), em nota à parte. Abreviaturas de termos consagrados pela Medicina deverão seguir as normas interna-cionais tradicionalmente em uso, de acordo com as abreviaturas padrões aprovadas pelo documento de Montreal, publicado no British Medical Journal, 1979;1:532-535.Nomes de Fármacos: Não é recomendável a utilização de nomes comerciais de fár-macos (marca registrada), mas quando a utilização for imperativa, o nome do produto deverá vir após o nome genérico, entre parênteses, em minúscula, seguido do símbolo que caracteriza marca registrada, em sobrescrito (®). Considerações Éticas e Legais: de acordo com Exigências para Manuscritos Submetidos a Revistas da área Biomédica (Comitê Internacional de Editores de Revistas Médicas – Fevereiro de 2006).

Conflito de InteressesO conflito de interesses existe quando um autor (ou a instituição do autor), revisor, ou editor tem relações de financiamento ou pessoais que influenciem de forma negativa (viés) suas ações. Essas relações variam desde com potencial mínimo até de grande potencial de influência sobre o julgamento, e nem todas representam conflito de inte-resses verdadeiro. O potencial para conflito de interesses pode existir se um indivíduo acredita ou não que suas relações afetam ou podem influenciar negativamente a credibi-lidade da revista, dos autores, ou da própria ciência. Entretanto conflitos podem ocorrer por outras razões, como relações pessoais, competição acadêmica e intelectual. Com isso, torna-se obrigatório o Author Agreement assinado por todos os autores.

Consentimento Livre e EsclarecidoOs pacientes têm direito à privacidade que não deve ser infringida sem consentimento livre e esclarecido. A identificação de informação, incluindo iniciais dos nomes dos pa-cientes, número de registro do hospital, não deve ser publicada através de descrições no texto, fotografias ou qualquer outra modalidade, a menos que ela seja essencial para os propósitos científicos e o paciente (ou responsável) forneça consentimento por escrito para publicação. O consentimento livre e esclarecido para esta finalidade exige que o paciente veja o manuscrito que será publicado. Os autores devem identi-ficar indivíduos que deram assistência na elaboração do texto e declarar a origem dos fundos para essa assistência.

Detalhes que facilitem a identificação devem ser omitidos se não forem essen-ciais. O anonimato completo é difícil de ser atingido, entretanto consentimento livre e esclarecido deve ser obtido se existir qualquer dúvida. Por exemplo, mascarar a região dos olhos em fotografia de pacientes é uma proteção inadequada para o anonimato. Se características de identificação forem alteradas para garantir o ano-nimato, os autores devem garantir que essas alterações não provocarão distorção do significado científico.

Quando o consentimento livre e esclarecido for obtido esta informação deve cons-tar da publicação.

ÉticaQuando estudos em humanos são publicados, os autores devem indicar se os procedi-mentos obedeceram aos padrões éticos do comitê de pesquisa em humanos (institu-cional ou nacional) e a Declaração de Helsinki de 1975, revista em 2000. Se existirem dúvidas quanto à condução de acordo com os padrões da Declaração de Helsinki, os autores devem explicar o racional para o procedimento e demonstrar que a comissão institucional responsável aprovou explicitamente os aspectos duvidosos do estudo. Quando a publicação for relativa à pesquisa com animais os autores devem indicar se foram obedecidas as normas de cuidados institucionais ou nacionais e o uso de animais de laboratório foi seguido.

Registro de Ensaio ClínicoEnsaios clínicos deverão ser registrados de acordo com orientação da OMS no endereço www.who.int/ictrp/en/. A OMS considera ensaios clínicos inclusive ensaios prelimi-nares (fase I), qualquer estudo que recrute prospectivamente sujeitos de pesquisa para serem submetidos a intervenções relacionadas à saúde (fármacos, procedimentos cirúrgicos, aparelhos, terapias comporta men tais, dietas, modificações nos cuidados de saúde) com finalidade de avaliar os efeitos sobre desfechos clínicos (qualquer variável biomédica ou relacionada com a saúde, inclusive medidas farmacocinéticas e efeitos adversos).

A revista tem o direito de não publicar estudos clínicos que não estejam de acordo com estes e outros padrões éticos determinados por diretrizes internacionais.

GUIDES FOR AUTHORS

Articles for publication shall be exclusively forwarded to Brazilian Journal of Anes-thesiology through http://ees.elsevier.com/bjan. Articles already published in other journals will not be accepted.

Brazilian Journal of Anesthesiology classifies the articles in the following categories:a) Scientific Articles: New clinical or experimental research information. b) Reviews: Summary of well established subjects, with a review of references and

conclusions, systematic review.c) Clinical Informations: Case reports, introduction of new techniques, methods and

equipments.d) Miscellaneous: Those not matching the above mentioned categories, but relevant

for Anesthesiology.e) Special Articles: Subject reviews relevant for Anesthesiology.f) Letters to the Editor: Constructive, objective and educational comments on publi-

shed matters. Discussions on Anesthesiology-specific subjects will by published on the sole Editor’s discretion.

g) Editorials.Publication Approval: All articles proposed for publication will be previously submit-ted to the analysis of two or more members of the Editorial Council or other Spe-cialized Consultants. When accepted, they will be subjected to minor corrections or changes which do not alter the author’s style. Possible modifications in format, style or interpretation will only be carried out after previous consultation. If denied, articles will be returned with a justification of the Editor-in-Chief. OBS: For final approval, author and co-authors shall sign a Record of Copyright As-

signment to Sociedade Brasileira de Anestesiologia and Elsevier Ed Ltda the content of which will be sent by the Editor-in-Chief.

Final Correction: Articles for publication will be forwarded, to the author, for due corrections and shall be returned as soon as possible. If there is a delay in returning the proof, the Editor-in-Chief has the right of publishing regardless of the final correction. The proof will be sent to the author whose address has been indicated for correspon-dence, remaining the said author responsible for the final appreciation of the subject and the others will agree with such publication.

Articles Presentation: Title: Article’s title shall be short, clear and straightforward to make easy its classifi-cation. When needed, a sub-title may be used. Author(s): Full name(s), their titles and affiliations in Societies or Institutions. Names of other collaborators may be mentioned at the end as acknow ledgments. A different paragraph shall be used to indicate the place where the study was carried out. Structured Summary: For scientific articles please state: Background and Objectives, Methods, Results and Conclusions. For clinical information please state: Background and Objectives, Case Report and Conclusions. For reviews please state: Background and Objectives, Contents and Conclusions. For all articles, inform Key Words for clas-sification according to Greene NM – Key Words in Anesthesiology, 3rd Ed, New York, Elsevier or newer.Text: without mentioning the author(s) or the place were it has been carried out. Scientific articles should have the following chapters: Introduction, Methods, Results, Discussion, Summary and References.References: The article shall contain only the references consulted, which shall be numbered as they enter the text. Other quotes of already numbered authors should indicate only the reference number; avoid mentioning the name of the author. The quotation of unpublished articles or presented in Medical Events is not recommen-ded. Text books and congress summaries references older than five years should be limited to those considered fundamental. When an article already accepted for publication is quoted, please include “to be published”, indicating the journal and the year. Personal communications will not be accepted. Use the model below: Journals: Author(s) names, middle name(s) initial(s) – paper’s title. Journal’s title

(abbreviated according to Index Medicus), year of publication; volume: number of first and last pages.

Pereira E, Vieira ZEG – Visita pré-anestésica, responsabilidade intransferível do anestesiologista. Rev Bras Anestesiol, 1977;27:337-353.

Books: Editor(s) name(s), middle name(s) initial(s) – book’s title (initials in capital letters), volume and edition, city of publication, Publisher, publication year and number of quoted page(s).

Rigatto M – Fisiopatologia da Circulação Pulmonar, 1ª Ed, São Paulo, Fundo Editorial Procienx, 1973;53-55.

Chapters: Author(s) name(s), middle name(s) initials – chapter title; editor(s) name(s), middle name(s) initials – Book title (initials in capital letters), volume and edition, city of publication, Publisher, publication year and quoted page(s).

Coelho A – Anatomia do Sistema Específico de Condução, em: Germiniani H – Diag-nóstico e Terapêutica das Arritmias Cardíacas. São Paulo, Fundo Editorial Procienx, 1972;3-10.

Note: Punctuation should never be used in names or abbreviations of mentioned publications. When there are less than three authors, all of them should be men-tioned; when there are more than three, only the first three should be mentioned, followed by the expression “et al.”.

Illustrations: Number illustrations according to text entry order. Number figures in Arabian numerals. Number charts and tables in Roman numerals. Indicate on the text the preferential site for the entry of each illustration (for example: Enter Figure x). Use black and white photos. The same result should not be expressed by more than

one illustration.Use of Digital Resources: Manuscript, Title Page, Cover Letter, and Author Agreement files in DOC format (Winword); bars or lines figures in XLS (Excell standard); photos and figures, with minimum re solution of 300 dpi, in JPG format. Please do not attach titles and letterings to illustrations. Please do not insert illustrations on text. Each illustration shall have an individual file. File name shall express illustration type and numbering (Figure 1, Table II, for example). Illustration titles and letterings duly num-bered shall be in separate text file. Copies or reproductions of other publications will be allowed only with the attachment of express authorization of the Editing company or the author of the original article.Abbreviations: Abbreviations are not recommended, except for those recog nized by the International System of Weights and Measures, or those widely accepted in medical publications. When there are large numbers of relevant abbre viations, their definitions should be presented in a separate note (Glossary). Abbreviations of well established medical terms should follow current traditional standards according to standard abbre-viations approved by the Montreal document published by the British Medical Journal, 1979;1:532-535.Drug Names: The use of commercial drug names (trademarks) is not re com mended, but when such use is mandatory, the product name should follow its generic name, in brackets, in lowercase, followed by the trademark symbol (®).Legal an Ethical Considerations: according with Uniform Requirements for Manus-cripts Submitted to Biomedical Journals (International Committee of Medical Journal Editors – February 2006).

Conflict of InterestConflict of interest exists when an author (or the author’s institution), reviewer, or editor has financial or personal relationships that inappropriately influence (bias) his or her actions (such relationships are also known as dual commitments, competing in-terests, or competing loyalties). These relationships vary from those with negligible potential to those with great potential to influence judgment, and not all relationships represent true conflict of interest. The potential for con flict of interest can exist whether or not an individual believes that the rela tionship affects his or her scientific judgment. Financial relationships (such as employment, consultancies, stock owner-ship, honoraria, paid expert testimony) are easily identifiable conflicts of interest and the most likely to under mine the credibility of the journal, the authors, and of science itself. However, conflicts can occur for other reasons, such as personal relationships, academic competition, and intellectual passion. For that reason, Author Agreement is a required document signed by all authors.

Informed ConsentPatients have a right to privacy that should not be infringed without informed con-sent. Identifying information, including patients’ names, initials, or hospital num-bers, should not be published in written descriptions, photographs, and pedi grees unless the information is essential for scientific purposes and the patient (or parent or guardian) gives written informed consent for publication. Informed consent for this purpose requires that a patient who is identifiable be shown the manuscript to be published. Authors should identify Individuals who provide writing assistance and disclose the funding source for this assistance.

Identifying details should be omitted if they are not essential. Complete ano ny mity is difficult to achieve, however, and informed consent should be obtained if there is any doubt. For example, masking the eye region in photographs of patients is inadequate protection of anonymity. If identifying characteristics are altered to protect anonymi-ty, such as in genetic pedigrees, authors should provide assurance that alterations do not distort scientific meaning and editors should so note.

When informed consent has been obtained it should be indicated in the published article.

Ethical TreatmentWhen reporting experiments on human subjects, authors should indicate whether the procedures followed were in accordance with the ethical standards of the responsi-ble committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. If doubt exists whe ther the research was conducted in accordance with the Helsinki Declaration, the authors must explain the rationale for their approach, and demonstrate that the institutional review body explicitly approved the doubtful aspects of the study. When reporting experiments on animals, authors should be asked to indicate whether the institutional and national guide for the care and use of laboratory animals was followed.

Clinical Trials RegistryClinical trial must be register according WHO recommendation at www.who.int/ictrp/en/. The definition of clinical trial include preliminary trials (phase I): any study with prospective recruiting of subjects to undergo any health-related inter vention (drugs, surgical procedures, equipment, behavioral therapies, food regi men, changes in health care) to evaluate the effects on clinical outcomes (any biomedical or health-related parameter, including pharmacokinetics measure ments and adverse reactions).

The Journal has the right of not publishing trials not complying with these and other legal and ethical standards determined by international guidelines.

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CONTRAINDICAÇÃO: Absolutas: hipersensibilidade à cetamina e porfiria. Relativas: Hipertensão arterial, antecedentes de acidente vascular cerebral e insuficiência cardíaca severa. INTERAÇÃO MEDICAMENTOSA: Pode prolongar o período de recuperação da anestesia dos hidrocarbonetos halogenados.

Referências Bibliográficas - 1. White PF, Schüttler J, Shafer A, Stanski DR, Horai Y, Trevor AJ. Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth. 1985;57(2):197-203. 2. Lauretti GR, Lima ICPR, Buscatti RY, Reis MP. Avaliação clínica dos efeitos hemodinâmicos, analgésicos, psicodélicos e do bloqueio neuromuscular da cetamina racêmcia e do seu S(+) isômero. Rev Bras Anestesiol, 2000; 50:5: 357-362. 3. Arendt-Nielsen L, Nielsen J, Petersen-Felix S, Schnider TW, Zbinden AM. Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain. Br J Anaesth. 1996;77(5):625-31. 4. Kanellopoulos A, Lenz G, Mühlbauer B. Stereoselective differences in the vasorelaxing effects of S(+) and R(-) ketamine on rat isolated aorta. Anesthesiology. 1998;88(3):718-24. 5. Ishizuka P, Garcia JBS, Sakata RK, Issy AM, Mülich SL. Avaliação da S (+) cetamina por via oral associada à morfina no tratamento da dor oncológica. Rev Bras Anestesiol. 2007; 57:1: 19-31. 6. Oliveira CMB, Sakata RK, TSA, Issy AM, Garcia JBS. Cetamina e analgesia preemptiva. Rev Bras Anestesiol. 2004; 54:5: 739-752.KETAMIN - cloridrato de dextrocetamina – 50mg/mL - INDICAÇÕES: agente anestésico único para pequenos procedimentos cirúrgicos ou diagnósticos que não necessitem relaxamento muscular esquelético; pode ser usado em doses adicionais para procedimentos mais prolongados; indutor anestésico quando da administração de outros agentes anestésicos gerais. Também é indicado para complementar a anestesia com agentes de baixa potência, tais como o óxido nitroso. Nas áreas de aplicações específicas ou tipos de procedimentos, incluem-se: procedimentos cirúrgicos em pacientes queimados, cirurgias superficiais, intervenções neurodiagnósticas, intervenções diagnósticas e cirúrgicas nos olhos, ouvidos, nariz e boca, intervenções diagnósticas e cirúrgicas na faringe, laringe ou árvore brônquica (com utilização de relaxante muscular), sigmoidoscopias, pequenas cirurgias do ânus e do reto e circuncisão, intervenções ginecológicas extraperitoniais (dilatação e curetagem), intervenções obstétricas (incluindo partos distócicos e cesarianas), intervenções ortopédicas, anestesia de pacientes de grande risco, com funções vitais deprimidas. Cateterismo cardíaco. CONTRAINDICAÇÕES: Absolutas: Hipersensibilidade a cetamina e porfiria. Relativas: Hipertensão arterial, antecedentes de acidente vascular cerebral e insuficiência cardíaca severa. CUIDADOS E ADVERTÊNCIAS: não utilizar o medicamento durante a gravidez e o período de amamentação. Nunca excluir o monitoramento dos sinais vitais. A função cardíaca deve ser continuamente monitorada durante o procedimento em pacientes predispostos a hipertensão ou descompensação cardíaca. Pode ocorrer depressão respiratória com uma superdosagem ou com a administração muito rápida. O Cloridrato de dextrocetamina deve ser usado por profissionais treinados na administração de anestésicos gerais, na manutenção das vias aéreas e no controle da respiração; deve-se dispor de equipamento de ressuscitação pronto para uso. A dose I.V. deve ser administrada num período de 60 segundos. O produto não deve ser utilizado como agente único em intervenções cirúrgicas ou diagnósticas da faringe, laringe ou árvore brônquica. Miorrelaxantes poderão ser necessários, devendo-se então prestar especial atenção à respiração. Não se deve empregar dextrocetamina como anestésico único nas intervenções obstétricas que exijam relaxamento do músculo uterino. Poderá ocorrer delírio durante o período de recuperação. Precauções para o período de recuperação: Para indício de reação psíquica durante o período de recuperação, considerar o uso de uma das seguintes drogas: diazepam (5 -10 mg para adultos por via I.V.) ou droperidol (2,5 - 7,5 mg por via I.V. ou I.M.). Pode-se administrar uma dose hipnótica de um tiobarbitúrico (50 -100 mg por via I.V.) para eliminar as reações graves da fase de recuperação. Ao se empregar qualquer uma dessas drogas, o período de recuperação pós-anestésica poderá se prolongar. INTERAÇÕES MEDICAMENTOSAS: Cloridrato de dextrocetamina é compatível com os anestésicos locais ou gerais de uso corrente, desde que mantida uma ventilação pulmonar adequada. As doses empregadas em associação com outros anestésicos variam nos limites das doses para indução de anestesia. A associação do produto com outro anestésico poderá permitir redução das doses. Potencializa os efeitos bloqueadores neuromusculares da tubocurarina. Pode prolongar o período de recuperação da anestesia dos hidrocarbonetos halogenados. A administração concomitante com barbitúricos e/ou narcóticos pode prolongar a fase de recuperação. Aumento do risco de hipotensão e/ou de depressão respiratória dos anti-hipertensivos ou depressores do SNC. Risco de hipertensão e taquicardia quando administrado em conjunto com hormônios da tireóide. Há incompatibilidade química entre os barbitúricos e a dextrocetamina ocorrendo formação de precipitado, não devendo ser injetados na mesma seringa. Os efeitos de dextrocetamina são potencializados pelo uso de diazepam; as duas drogas devem ser administradas separadamente. REAÇÕES ADVERSAS: manifestações fisiológicas acontecem na fase de emergência da anestesia e variam entre sonhos agradáveis, imagens vividas, alucinações e delírio. Estas reações da emergência ocorrem em frequência muito menor do que no uso da mistura racêmica. Cardiovasculares: pode ocorrer aumento da pressão arterial e da frequência cardíaca, hipotensão, bradicardia, arritmia cardíaca. Respiratórias: Poderá ocorrer depressão ou apneia, após a administração I.V. rápida de doses elevadas de dextrocetamina. Têm sido observados casos de laringoespasmo e outras formas de obstrução das vias respiratórias durante a anestesia. Neurológicos: Há relatos de pacientes com movimentos tônicos e clônicos, que às vezes assemelham-se a convulsões. Esses movimentos não implicam num plano superficial de anestesia. POSOLOGIA: Pré-Operatório: KETAMIN pode ser empregado como agente único, sem nenhum risco, ainda que o paciente não esteja em jejum se, a critério do médico, os benefícios decorrentes do uso do produto forem maiores do que os possíveis riscos. Uso Pediátrico: Doses intramusculares, nos limites de 9 a 13 mg/kg, normalmente produziram anestesia cirúrgica dentro de 3 a 4 minutos após a injeção, com efeito anestésico de 12 a 25 minutos de duração. Indução: Via Intravenosa: A dose inicial de KETAMIN administrada intravenosamente pode variar entre 1 mg/kg a 4,5 mg/kg. Recomenda-se que o produto seja administrado lentamente num período de 60 segundos. Alternativamente, em pacientes adultos, pode ser usada na indução de anestesia, dose intravenosa de 1 mg a 2 mg/kg de KETAMIN, numa velocidade de 0,5 mg/kg/minuto. Via Intramuscular: A dose inicial de KETAMIN administrada intramuscularmente pode variar entre 6,5 a 13 mg/kg. A dose de 10 mg/kg normalmente produz anestesia cirúrgica de 12 a 25 minutos de duração. Manutenção da Anestesia: A anestesia é mantida pela administração de doses adicionais de KETAMIN por via intravenosa ou por via intramuscular, independentemente da via empregada para indução. Quanto maior for a dose administrada de KETAMIN tanto maior será o tempo de recuperação. Dosagem: A droga deve ser titulada conforme a necessidade do paciente, levando-se em consideração que a dextrocetamina é 2 vezes mais potente do que a mistura racêmica da cetamina. Diluição: Para o preparo de uma solução diluída contendo 1 mg de dextrocetamina por mL, transferir assepticamente 10 mL (50 mg/mL do frasco-ampola) e diluir para 500 mL de glicose 5% ou cloreto de sódio 0,9% e misturar bem. Se a restrição do fluído for necessária, a diluição pode ser feita em 250 mL, resultando dessa forma em 2 mg de dextrocetamina por mL. SUPERDOSAGEM: pode ocorrer depressão respiratória após dose excessiva de dextrocetamina. A utilização de ventilação mecânica, que mantenha uma saturação adequada do oxigênio sanguíneo e eliminação de dióxido de carbono, é preferível ao emprego de analépticos. Cloridrato de dextrocetamina oferece ampla margem de segurança. Doses excessivas acidentais de até 10 vezes maiores que as habituais têm sido seguidas de recuperação prolongada, porém completa. CRISTÁLIA - Produtos Químicos Farmacêuticos Ltda - Farm. Resp.: Dr. José Carlos Modolo - CRF-SP nº 10.446 - Rod. Itapira-Lindóia, km 14 - Itapira-SP - CNPJ Nº 44.734.671/0001-51 - SAC 0800-7011918 - Nº do Lote, Data de Fabricação e Prazo de Validade: Vide Rótulo e Caixa - CLASSIFICAÇÃO: VENDA SOB PRESCRIÇÃO MÉDICA - RESTRITO A HOSPITAIS – SOB RETENÇÃO DE RECEITA – Reg. MS nº 1.0298.0213 - SE PERSISTIREM OS SINTOMAS, O MÉDICO DEVERÁ SER CONSULTADO.

AMPOLAS / FRASCOS

• Estojos de acordo com a RDC 71 que estabelece o padrão de apresentação

dos rótulos e cartuchos.1

• Facilita a conferência da substância, concentração e via de administração da droga a ser administrada. • Menor risco de erro de medicação.2,3

• Atende às recomendações da Sociedade Brasileira de Anestesiologia para Segurança em Anestesia Regional.4

Referências Bibliográfi cas: 1.Brasil. Resolução RDC Nº 71, de 22 de dezembro de 2009. Estabelece re-gras para a rotulagem de medicamentos. Diário Ofi cial da União, Brasília, 23 de dezembro de 2009, seção 1, p. 75-80. 2. Gouveia MA, Mauro CL, Amaral A. Injeção Inadvertida de galamina no espaço subaracnóideo. Relato de um caso. Rev Bras Anestesiol 1983. 33, 3.189 – 192. 3. Vieira ZEG. Complicações da Anestesia Raquídea. Rev Bras Anestesiol 1963; 13:77-81. 4. Fernandes, Fonse-ca, Rosa Et Al. Brazilian Society Of Anesthesiology Recommendations For Safety In Regional Anesthesia. Rev Bras Anestesiol, 2011; 61(5):679-694.

•AF_21x28cm_ SterliePack 5_ 11ABR.indd 1 11/04/12 22:39

1. Baker et al. Anesth Analg 2007; 104: 1447-51 2. Lançado em dezembro de 2005 nos Estados Unidos.

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POR QUE TERA A INVENTORA1 DOSEVOFLURANOCOMO PARCEIRA

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COMO PARCEIRA

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Revista Brasileira de Anestesiologia IVol. 64, No 1, January-February, 2014

The Brazilian Journal of Anesthesiology is indexed by Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) since 1989,Excerpta Médica database-EMBASE since 1994, Scientific Electronic Library Online (SciELO – Brasil) since 2002,

MEDLINE since 2008, Science Direct since May 2010 and ISI Web of KnowledgeSM since March 2011.

A Revista Brasileira de Anestesiologia é indexada na Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) desde 1989, na Excerpta Médica database-EMBASE desde 1994, no Scientific Electronic Library Online (SciELO – Brasil) desde 2002,

no MEDLINE desde 2008, no Science Direct desde 2010 e ISI Web of KnowledgeSM desde março de 2011.

Scientific Special / Artigos Especiais001 SBA Recommendations for regional anesthesia safety in patients taking anticoagulants Recomendações da SBA para segurança na anestesia regional em uso de anticoagulantes Neuber Martins Fonseca, Rodrigo Rodrigues Alves, João Paulo Jordão Pontes e Sociedade Brasileira

de Anestesiologia

016 Premedication with midazolam prior to caesarean section has no neonatal adverse effects A pré-medicação com midazolam antes de secção cesariana não tem efeitos adversos no neonato Ahmet Can Senel, Fatih Mergan

022 Preoperative evaluation of the patient with pulmonary disease Avaliação pré-operatória do paciente pneumopata Luiza Helena Degani-Costa, Sonia Maria Faresin, Luiz Fernando dos Reis Falcão

Scientific Articles / Artigos Científicos035 Do metoclopramide and ondansetrone alter mivacurium-induced neuromuscular blockade?

a randomised trial Metoclopramida e ondansetrona alteram o bloqueio neuromuscular induzido por mivacúrio?

um estudo randomizado Mehmet Tercan, Esra Mercanoglu Efe, Gurkan Turker, Fatma Nur Kaya, Belgin Yavascaoglu, Yesim Ozarda,

Elif Basagan Mogol

040 Intravenous clonidine administration and its ability to reduce pulmonary arterial pressure in patients undergoing heart surgery

Administração de clonidina intravenosa e sua capacidade de reduzir a pressão da artéria pulmonar em pacientes submetidos a cirurgia cardíaca

Benedito Barbosa João, José Luis Gomes do Amaral, Ronaldo Machado Bueno, David Ferez, Luiz Fernando dos Reis Falcão, Marcelo Vaz Perez, Itamar Souza de Oliveira-Júnior

049 Determination of the minimum effective volume of 0.5% bupivacaine for ultrasound-guided axillary brachial plexus block

Determinação do volume mínimo efetivo de bupivacaína 0,5% para bloqueio do plexo braquial por via axilar guiado por ultrassom

Leonardo Henrique Cunha Ferraro, Alexandre Takeda, Luiz Fernando dos Reis Falcão, André Hosoi Rezende, Eduardo Jun Sadatsune, Maria Angela Tardelli

ISSN 0034-7094 • Volume 64/Volume 64 • Número 1/Number 1 • Janeiro-Fevereiro/January-February, 2014

Revista BRasileiRa de anestesiologia

Órgão oficial da

Departamento de Anestesiologia da Associação Médica Brasileira

II Revista Brasileira de Anestesiologia Vol. 64, No 1, January-February, 2014

054 Indication of preoperative tests according to clinical criteria: need for supervision Indicação de exames pré-operatórios segundo critérios clínicos: necessidade de supervisão Aline Pallaoro Garcia, Karen Adriana Pastorio, Rodrigo Lopes Nunes, Giovani Figueiredo Locks,

Maria Cristina Simões de Almeida

062 Effectiveness of the C-MAC video laryngoscope in the management of unexpected failed intubations Efi cácia do videolaringoscópio C-MAC no manejo de intubações malsucedidas inesperadas Alper Kilicaslan, Ahmet Topal, Aybars Tavlan, Atilla Erol, Seref Otelcioglu

Miscellaneous / Artigo Diverso066 Can supreme™ laryngeal mask airway be an alternative to endotracheal intubation in laparoscopic

surgery? A máscara laríngea supreme™ pode ser uma opção para a intubação endotraqueal em cirurgia

laparoscópica? MeltemTurkayAydogmus,HacerSebnemYeltepeTurk,SibelOba,OyaUnsal,SıtkıNadirSınıkoglu

Letter to the Editor / Carta ao Editor071 The use of laryngeal mask airway in tonsillectomies Uso de máscaras laríngeas em tonsilectomias Alper Nabi Erkan

072 Reply to Alper Nabi Erkan Resposta a Alper Nabi Erkan Dante Ranieri Junior

Rev Bras Anestesiol. 2014;64(1):1---15

REVISTABRASILEIRA DEANESTESIOLOGIA Official Publication of the Brazilian Society of Anesthesiologywww.sba.com.br

SCIENTIFIC ARTICLE

SBA Recommendations for regional anesthesia safety in patientstaking anticoagulants

Neuber Martins Fonseca, Rodrigo Rodrigues Alves, João Paulo Jordão Pontes,Sociedade Brasileira de Anestesiologia ∗

School of Medicine, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil

Received 23 April 2013; accepted 28 April 2013

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Description of evidence collection method

We conducted searches in multiple databases (Medline1965-2012; Cochrane Library, Lilacs) and cross-referenceswith the collected material to identify studies with bettermethodological design, followed by a critical evaluation oftheir contents and classification according to the strengthof evidence.

We conducted searches between August and December2012. The following strategies were used for searches inPubMed:

1. ‘‘regional anaesthesia’’ OR ‘‘anesthesia, conduction’’OR ‘‘anesthesia’’ AND ‘‘conduction’’ OR ‘‘conductionanesthesia’’ OR ‘‘regional’’ AND ‘‘anesthesia’’ OR‘‘regional anesthesia’’ AND ‘‘antithrombotic’’;

2. ‘‘regional anaesthesia’’ OR ‘‘anesthesia, conduc-tion’’ [MeSH Terms] AND ‘‘infection’’ [MeSHTerms] AND ‘‘thromboembolism’’ [MeSH Terms] OR‘‘thromboembolism’’ [All Fields];

3. ‘‘thromboembolism’’ [MeSH Terms] OR

‘‘thromboembolism’’ [All Fields] AND ‘‘regional anaes-thesia’’ [All Fields] OR ‘‘anesthesia, conduction’’ [MeSHTerms] OR ‘‘anesthesia’’ [All Fields] AND ‘‘conduction’’

∗ Corresponding author:E-mail: sba@sba.com.br

( Sociedade Brasileira de Anestesiologia).

O

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0104-0014/$ – see front matter © 2013 Sociedade Brasileira de Anestesiohttp://dx.doi.org/10.1016/j.bjane.2013.04.010

[All Fields]) OR ‘‘conduction anesthesia’’ [All Fields] OR‘‘regional’’ [All Fields] AND ‘‘anesthesia’’ [All Fields]OR ‘‘regional anesthesia’’ [All Fields].

In the field of regional anesthesia, we selected stud-es addressing managements of different types of regionalnesthesia in individuals taking drugs that modify the bloodoagulation status. We focused on risk factors, etiology, pre-ention, diagnosis, and treatment. We also included studiesssessing the risk of complications in patients after regionallockade and studies that clarify the management and safeandling of drugs to be administered.

evel of evidence and strength ofecommendation

A: Experimental or observational studies with better con-sistency.B: Experimental or observational studies with less consis-tency.C: Case reports or case series (non-controlled studies).D: Opinion without critical evaluation, based on consensus,expert opinions, physiological studies, or animal models.

bjective

o assess the safety aspects of regional anesthesia andnalgesia, such as the possible technique’s complications;

logia. Published by Elsevier Editora Ltda. All rights reserved.

dx.doi.org/10.1016/j.bjane.2013.04.010http://www.sba.com.brmailto:sba@sba.com.brdx.doi.org/10.1016/j.bjane.2013.04.010

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isk factors associated with spinal hematoma, preventiontrategies, diagnosis, and treatment; and safe interval forrug suspension and resumption after regional block inatients taking antithrombotic drugs.

ntroduction

he current incidence of neurological dysfunction resultingrom bleeding complications associated with neuraxial blocks unknown.1 Its occurrence is estimated to be less than:150,000 epidural punctures and 1:220,000 subarachnoidunctures.1 After neuraxial anesthesia, the use of anti-oagulants is the risk factor most often associated withpinal hematoma.2 Because spinal hematoma is rare, recom-endations regarding regional anesthesia and concomitant

se of thromboprophylaxis or antithrombotic therapy, whichould be of greater predictive value if reported by prospec-

ive randomized studies, are based on case reports andxpert recommendations3, which ethically precludes thetudy.

The number of patients on anticoagulant therapy haseen growing due to the aging process, longer lifexpectancy, and prevalence of cardiovascular disease.ecommendations on safety in regional anesthesia andntithrombotic therapy should be constantly updated, as thentroduction of new antithrombotic drugs to the market isone at regular intervals.2

This guideline aims to review the risks and recommenda-ions for regional anesthesia in subjects taking drugs thatnterfere with coagulation and present safety regulationsnd guidelines required for regional procedures.

pinal/epidural hematoma

ncidence

lthough the incidence of spinal-epidural hematoma (SEH)s small, the clinical severity of its consequences, along withitigation costs that follow an adverse event, makes it crucialo develop sound strategies for the management of patientsn anticoagulants during neuraxial anesthesia.4

In a literature review5 assessing several case reports, weoted that the incidence of SEH was 1:220,000 after spinalnesthesia and 1:150,000 after epidural puncture. However,ecent indications suggest a higher incidence, as the stud-es used in these calculations were conducted before theerioperative thromboprophylaxis routine.6

After the introduction of enoxaparin (30 mg, twice daily)or thromboprophylaxis in the United States, an alarmingumber of cases of epidural hematoma, some with perma-ent paraplegia, the risk of spinal/epidural hematoma withwice daily administration of enoxaparin was reported andalculated at 1:40,800 after spinal anesthesia, 1:6,600 afterimple epidural puncture, and 1:3,100 after epidural punc-ure with epidural catheter insertion.7 In Europe, a singleose administration of enoxaparin (40 mg) showed a lowerncidence of spinal hematoma. In a retrospective Swedish

tudy,8 the authors found a risk of 1:156,000 after spinalnesthesia and 1:18,000 in epidural anesthesia. Bleedingas rare in the obstetric population (1:200,000) comparedith that of women undergoing knee arthroplasty (1:3,600).

mdbe

N.M. Fonseca et al.

ubsequent studies showed incidences as high as 1:2,700o 1:19,505.9---11 However, Cook et al. presented updatedesults at the Third National Audit Project of the Royal Col-ege of Anaesthetists in which only eight cases of SEH wereeen in 707,405 neuraxial blocks. Of these, only five methe inclusion criteria, and the incidence was calculated at:88,000 to 1:140,000.12

isk Factors2,4

he occurrence of SEH is more spontaneous than the resultf neuraxial anesthesia. Most spontaneous hematomas arediopathic; cases related to anticoagulant therapy and vas-ular malformations are the second and third most commonauses, respectively. Concomitant use of anticoagulants ishe main risk factor related to SEH, when associated witheuraxial block.2

Risk factors for SEH have been described by severaluthors8,13---18 and are shown in Table 1. The incidence ofEH varies according to the type of surgery, age and genderf patient. For example, the incidence of SEH in obstet-ic surgery is estimated at 1:200,000, whereas in geriatricge women undergoing knee arthroplasty it is estimated at:3,600.8 This may be explained by the higher incidencef spinal abnormalities associated with osteoporosis, use ofual antiplatelet/anticoagulant therapy, and accumulationf anticoagulant due to a decrease in renal excretion notetected in this age group.

Among the type of neuraxial blocks, the risk of SEH isigher with the use of epidural catheters, followed by simplepidural puncture, and less frequent after single subarach-oid puncture,17,19,20 the latter likely due to the thinnereedles used in the technique. Catheter removal is as crit-cal as insertion; therefore, vascular injury may still occur4

t the same incidence; that is, half the cases of SEH occursuring epidural catheter removal.16

There are indications that epidural hematoma is moreommon after lumbar puncture compared with thoracicuncture.11

linical condition, treatment, and prevention

leeding into the spinal canal, which causes thecal sacompression, may result in irreversible neurological damageith paraplegia and is a major concern of anesthesiolo-ists performing neuraxial block in patients on anticoagulantrugs.4

Clinical condition is characterized by slow regression orbsent sensory or motor block, back pain, urinary reten-ion or return of motor or sensory deficit after completeegression of the previous block, alone or in combination,uggesting the development of spinal hematoma.2

In the presence of clinical suspicion of spinal hematoma,n aggressive diagnostic and therapeutic approach is manda-ory. This includes emergency nuclear magnetic resonancemaging (NMRI) or, if unavailable, computed tomographyCT). Because SEH is a neurosurgical emergency, protocols

ust be established to avoid any delay in diagnosis. Onceiagnosis is confirmed, decompressive laminectomy shoulde performed within 6-12 hours after the onset of symptoms,nabling chances of neurological recovery.16,21

SBA Recom

mendations

for regional

anesthesia safety

in patients

taking anticoagulants

3

Table 1 Risk Factors Associated with Hematoma Spinal/Epidural.

1 --- Patient-relateda. Age (elderly);b. Female;c. Congenital coagulopathies;d. Acquired coagulopathies (renal/hepatic malignancies, HELLP syndrome (hemolysis, elevated liver enzymes, low platelet

count), disseminated intravascular coagulation [DIC]);e. Thrombocytopenia;f. Spinal abnormalities (spina bifi da/spinal stenosis, osteoporosis, ankylosing spondylitis).2 --- Procedure-relateda. Insertion or removal of the catheter;b. Traumatic procedure (multiple attempts);c. Presence of blood in the catheter during insertion or removal;d. Epidural catheter insertion > Simple epidural puncture > Simple spinal puncture.3 --- Drug-relateda. Anticoagulant drugs, antiplatelet or fi brinolytic;b. Administration of the drug immediately before/after neuraxial technique;c. Use of antiplatelet therapy/dual anticoagulant.

Drugs Recommendations

ASA and NSAIDs There is no indication of suspension.ASA and NSAIDs +

LMWH/UFH/coumarinWait 24 hours for neuraxial block or epidural catheter insertion.

ASA + thienopyridine If the patient is using metallic stent, wait 6 weeks. If the stent is pharmacological, wait 6 months.Ticlopidine Perform blockade or insertion/removal of catheter 10-14 days after suspension.Clopidogrel Perform blockade or insertion/removal of catheter 7 days after

suspension. In high risk patients, it may be performed in 5 days.Prasugrel Perform neuraxial block 7-10 days after drug discontinuation.Abciximab Perform neuraxial block or insertion/removal of catheter 48 hours after drug discontinuation.Tirofi ban/eptifibatide Wait 8-10 hours to perform neuraxial block or epidural catheter insertion.Glycoprotein IIb/IIIa inhibitors

+ other anticoagulants/AASContraindication for blockade.

Ticagrelor Perform blockade or insertion/removal of catheter 5 days after drug discontinuation.Cilostazol Perform blockade or insertion/removal of catheter 5 days after drug discontinuation.Unfractionated heparin Wait 4 hours after the last dose of UFH for blockade, removal/insertion of catheter. Restart drug after 1 hour.

4

N.M

. Fonseca

et al.

Table 1 (Continued )

Drugs Recommendations

Low molecular weight heparin Prophylactic doses: wait 10-12 hours to perform blockade.Therapeutic doses: wait 24 hours. Withdrawal of catheter 10-12hours after last dose. Restart drug 2 hours after catheter removal.

Coumarin Perform blockade 4-5 days after discontinuation. INR monitoringduring epidural analgesia.

Fondaparinux Prophylactic dose (2.5 mg): blockade may be performed. If epiduralcatheter, remove it 36 hours after the last dose. Restart dose 12hours after catheter removal. Therapeutic dose (5-10 mg): blockade is contraindicated.

Rivaroxaban Perform neuraxial blockade, insertion/removal of catheter 24 hoursafter drug discontinuation. Restart 4-6 hours after catheter removal.

Apixaban Perform neuraxial blockade, insertion/removal of catheter 20-30hours after drug discontinuation. Restart 4-6 hours after catheter removal.

Desirudin Perform blockade 8-10 hours after drug discontinuation in patients with normal renal function.

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Thus, patients should be carefully evaluated to investi-gate possible signs indicating SEH, both after neuraxial blockand epidural catheter removal. The patient should be mon-itored at regular intervals until regression of sensory blockby at least two dermatomes or motor function recovery2 andfor at least 24 hours after epidural catheter removal.21

European and American societies have published guide-lines with the goal of increasing security in performingneuraxial block in patients on anticoagulants.1,6,22---27 How-ever, most of these recommendations are expert opinionsbased on case series and pharmacological data withanticoagulant drugs involved.27 These recommendationsinclude: (I) minimum time interval required between thelast dose of anticoagulant and the insertion of neurax-ial needle/catheter or catheter removal; (II) minimuminterval required between the insertion of neuraxialneedle/catheter or catheter removal and next dose of anti-coagulant; (III) minimum coagulation time required for theuse of neuraxial technique (if available for the drug beingused).

Due to the rapid development of anticoagulant drugs bythe pharmaceutical industry and their release and increas-ing use in clinical practice, experiments are lacking andit becomes difficult to make any statement on the use ofneuraxial anesthesia in patients on new anticoagulants.

Recently, Rosencher et al. proposed a new strategy formanaging patients on new anticoagulants.28 According tothis strategy, the insertion and subsequent withdrawal ofneuraxial needle/catheter must be made at a time superiorto two half-lives of elimination after the last dose of theused anticoagulant. The basis for this proposal is that 30%to 40% of the function of coagulation factors is required forhemostasis, so that after two half-lives, the drug concen-tration in bloodstream is near 25% of the initial. The nextanticoagulant dose should be administered with a time inter-val (dT) obtained by subtracting the time needed for thedrug to reach the peak plasma level and the time to producestable blood clot, considered 8 hours (8h-Tpeak = dT).28

Neuraxial block and use of antiplatelet agents

Antiplatelet drugs consist of non-steroidal anti-inflammatory drugs (NSAIDs), thienopyridines (ticlopidine,clopidogrel, and prasugrel), and glycoprotein IIb/IIIainhibitors (abciximab, eptifibatide, and tirofiban).

Acetylsalicylic acid (ASA) and NSAIDs

ASA promotes irreversible blockade of platelet function byinhibiting cyclooxygenase enzyme production of thrombox-ane A2 (potent platelet activator). This effect lasts the sameas the platelets’ half-life, usually 7-10 days.3

Other NSAIDs also inhibit cyclooxygenase-1 and plateletaggregation, but in a reversible manner and proportionalto the agent half-life. This process normalizes from 12to 24 hours after NSAIDs discontinuation.29 The selectiveinhibitors of Type 2 cyclooxygenase (COX-2) are anti-

inflammatory drugs that do not cause platelet dysfunction,as COX-2 is not expressed in platelets.30

The bleeding effect caused by ASA appears to be dose-dependent, with more marked effects in patients receiving

3

taking anticoagulants 5

oses greater than 100 mg.day-1 31 However, prospectivetudies evaluating the safety of neuraxial block with ASAeported no case of spinal hematoma.32---34

Although the isolated use of ASA seems not to increasehe probability of spinal hematoma, complications haveeen observed in both medical and surgical patients, ifombined with heparin.14,35 Thus, in individuals using ASA,t seems prudent to administer heparin for postopera-ive thrombosis prophylaxis, as the research team did notbserve superiority of thromboprophylaxis when the heparinose is given preoperatively (B).36 However, the administra-ion of a low-dose combination of ASA-dipyridamole seemsot to increase the risk of spinal hematoma.2

In patients with a history of acute coronary syndromeACS), cerebrovascular accident (CVA) or peripheral arterialcclusive disease, ASA reduces the risk of recurrent car-iovascular events by 30% and mortality by approximately5%.37 Recent studies suggest that morbidity and mortal-ty, particularly in patients with newly implanted coronarytents or unstable coronary syndrome is markedly increasedf ASA is suspended before a surgical procedure.38---40

ebound phenomenon has also been described.41 The riskf late thrombosis is higher in patients with drug-elutingtents.

In summary, the perioperative suspension of ASA is unnec-ssary in most cases and associated with an increased riskf acute thrombosis. We recommend that patients withCS or stent should continue taking ASA throughout life.42

he American College of Chest Physicians (ACCP) does notecommend platelet function evaluation prior to invasiverocedures because there is no apparent correlation withleeding (D).43

ecommendations

. NSAIDs appear to represent no significant additional riskfor the onset of spinal hematoma in patients undergo-ing epidural or spinal anesthesia. NSAIDs (including ASA)have no risk level that interferes with the performance ofneuraxial blocks. In patients on these medications, thereis no specific concern regarding the interval betweenspinal/epidural puncture or catheter insertion and thelast dose of the given drug, or the need for postoperativemonitoring and interval for catheter removal or postop-erative drug administration (A).6,32---34

. Concomitant use of medications affecting other clot-ting mechanism components, such as oral anticoagu-lants, unfractionated or low molecular weight heparinincreases the risk of bleeding complications in patientson NSAIDs. In these patients on ASA, the administration ofheparin dosage for postoperative thromboprophylaxis isrecommended (B).36 In these patients, if low molecularweight heparin (LMWH) is administered preoperatively,there should be a 24-hour wait period before performingblockade or removing the epidural catheter due to theincreased risk of bleeding (C).6

. Cyclooxygenase Type 2 inhibitors (COX-2) have mini-mal effect on platelet function and should be preferredin patients who need anti-inflammatory therapy in thepresence of anticoagulation (D).6 There is no evidence

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supporting the effect on the ability of platelet aggrega-tion or increased tendency to bleeding (D).1

. In patients with coronary stent receiving dual platelettherapy (ASA + thienopyridine), needing surgery, andrequiring surgical procedure, we recommend postpon-ing surgery for at least 6 weeks in the case of metallicstents and at least 6 months in case of drug-elutingstents (D).43 If patients need surgery within 6 weeks aftermetallic stent or 6 months after drug-eluting stent, dualantiplatelet therapy should be maintained, and regionalanesthesia is contraindicated via neuraxial route (D).43

. Analgesics, such as paracetamol and dipyrone, are not acontraindication for neuraxial regional anesthesia, inso-far there are no cases related to spinal hematoma (D).3

hienopyridines

iclopidine (Ticlid®), clopidogrel (Plavix®), and prasugrelEfient®) are platelet inhibitors belonging to the class ofhienopyridines. They are prodrugs cleaved in vivo in theiver to active metabolites that antagonize the plateleteceptor of adenosine dinucleotide phosphate (ADP) (P2Y12)nd interfere with platelet activation and aggregation, anffect that can not be antagonized and is irreversible.1,2

There is no prospective study assessing the safety ofeuraxial techniques in subjects under treatment withhienopyridines. However, cases of spinal hematoma haveeen reported after neuraxial anesthesia in patients takinghese drugs.44

iclopidine (Ticlid®)

iclopidine half-life is 30 to 50 hours, which increases up to6 hours if used routinely for more than 14 days.2 Plateletysfunction with the use of ticlopidine remains for 10 to 14ays after drug discontinuation.1 Unlike clopidogrel, ticlo-idine may lead to neutropenia in more than 1% of patients,hich is a limiting factor of its use.3

ecommendations

euraxial block or epidural catheter removal can only beerformed after 10-14 days of ticlopidine suspension (D).3,6

lopidogrel (Plavix®)

lopidogrel half-life is 120 hours. However, its activeetabolite half-life is only 8 hours.2 The platelet functionaximum inhibition of oral clopidogrel (75 mg) occurs within

-7 days or about 12-24 hours after an initial loading dosef 300-600 mg. Recovery of platelet function occurs only-7 days after the end of clopidogrel administration.45 Inatients at high risk for angina, discontinuation for five daysas been suggested to prevent cardiovascular morbidity.46

ecommendations

euraxial blockade or removal of epidural catheter inatients on clopidogrel should only be performed after ateast seven days of drug discontinuation (D).3 In the case of

N.M. Fonseca et al.

atients with high risk of angina recurrence, the interval ofve days suspension has been suggested (D).6

rasugrel (Efient®)

novel thienopyridine that, similar to others, depends onepatic conversion to active metabolite to bind to platelet2Y12 receptor (which binds to ADP for platelet activation)nd perform its inhibitory activity. This drug has a rapidnset of action (30-60 minutes) and is 10 times more potenthan clopidogrel.47 The antiplatelet effect is equal to the lifef platelet, and pretreatment platelet function is restored-10 days after drug discontinuation.3

One study comparing prasugrel and clopidogrel in 13,608atients with acute coronary syndrome undergoing percu-aneous coronary intervention showed significant reductionf ischemic events treated with prasugrel, but also a highernd occasionally fatal risk of bleeding.48

ecommendations

here is no available study assessing the combination ofrasugrel and neuraxial anesthesia. However, it seems rea-onable that treatment with prasugrel be discontinued ateast 7-10 days before neuraxial block or removal of epiduralatheter (D).3

lycoprotein IIb/IIIa inhibitors

lycoprotein IIb/IIIa inhibitors include abciximabReopro®), eptifibatide (Integrilin®), and tirofibanAggrastat®). Currently, these agents are the mostffective drugs available for platelet aggregation inhibi-ion, as they block the platelet glycoprotein IIb/IIIa (theite of fibrinogen binding between platelets), which is thenal common pathway of platelet aggregation.2 These drugsre only available for intravenous use. Antiplatelet effectsre reversible and disappear after the discontinuation ofptifibatide, tirofiban, and abciximab within 8, 24, and8 hours, respectively. The most common side effects arehrombocytopenia and bleeding,50 expressed in 0.3-1%ith abciximab.49 Abciximab showed better efficacy than

irofiban and eptifibatide.51

ecommendations

. According to the pharmacological properties of thesedrugs, insertion of epidural/spinal needle/catheter orcatheter removal should only be performed after com-plete recovery of platelet aggregation; that is, withdiscontinuation of 8-10 hours for tirofiban/eptifibatideand 48 hours for abciximab and exclusion of any throm-bocytopenia through a recent platelet count (D);2

. GP IIb/IIIa inhibitors are used in acute coronary syn-

drome, in combination with anticoagulants and ASA. Inthis scenario, any neuraxial blockade is contraindicatedin emergency procedures that usually involve cardiacsurgery with continued anticoagulation (D).3

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Other antiplatelet

Ticagrelor (Brilinta®)

Unlike thienopyridines, ticagrelor acts directly on P2Y12receptor and does not require liver biotransformation intoactive metabolites by cytochrome P450, although metabo-lites are also active. Similar to prasugrel, ticagrelor providesa very fast (< 2 h), intense (about 70%), and consistentinhibition of P2Y12 receptor, which is greater than thatof clopidogrel (30-40%).47 It has a rapid onset of actionwith reversible binding and short duration (48-72 h), andrequires oral administration in two doses. The initial effecton platelet aggregation is seen 30 minutes after loadingdose. With treatment discontinuation, platelet function isrestored within 4-5 days.52

Recommendations

There is no available data regarding the perioperativeuse of this agent. Theoretically, its short and reversibleantiplatelet effect can facilitate perioperative manage-ment. However, neuraxial anesthesia should be discouragedduring treatment with ticagrelor, unless it is suspended forat least five days before the anesthetic procedure, so thatplatelet function can return to normal (D).3

Cilostazol (Vasogard®, Cebralat®, Pletal®)

Cilostazol provides selective inhibition of phosphodiesteraseIIIa (PDEIIIa); thus, it increases the level of intracellu-lar cyclic adenosine monophosphate (cAMP) and leads toweak platelet aggregation inhibition.53,54 Because vascu-lar smooth muscle contains PDEIIIa, cilostazol also providesdirect arterial vasodilation. Nevertheless, cilostazol mech-anism of action is not fully understood. Its use is indicatedfor peripheral arterial disease and intermittent claudicationin individuals who do not respond to exercise therapy andthose with low possibility of surgical intervention.55

The route of administration is orally at a dose of 100 mgtwice daily, and peak plasma level is achieved within 2.7 to3.6 hours. Drug compound is mainly eliminated by hepaticmetabolism and subsequent urinary excretion of metabo-lites. The terminal elimination half-life of cilostazol and itsactive metabolites is approximately 21 hours, and some of itsmetabolites inhibit platelet aggregation at a higher intensitythan the parent compound.54

A recent case report found spinal hematoma after epidu-ral catheter removal during treatment with cilostazol,56 but,in general, there is no prospective data on this drug’s periop-erative use and its effect on bleeding incidence is unknown.

Recommendations

Neuraxial block and catheter removal may be performedconsidering the minimum clearance interval of two half-

lives between blockade and the last dose of cilostazol (i.e.,42 hours), although laboratory recommendation is five daysof suspension.3 The next dose of cilostazol should only beadministered 5 hours after catheter removal (D).28,57

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eparins

nfractionated heparin (UFH)

he major anticoagulant effect of heparin is due to pen-asaccharide present in one third of heparin molecules,hich binds to antithrombin III (ATIII).6 After this binding,FH catalyses the inactivation of IIa (thrombin), IXa, and Xa,nd, to a lesser extent, XIa and XIIa factors.4 In the absencef heparin, antithrombin III has low affinity for thrombin.owever, when UFH binds to ATIII, the thrombin-bindingate accelerates from 100 to 1,000 times, similarly to otheroagulation factors inhibited by it. UFH also binds stronglyo several plasma proteins, endothelial cells, macrophages,nd platelet factor 4 (PF4), which results in low bioavail-bility, inaccurate pharmacokinetics, and heparin-inducedhrombocytopenia (HIT).58

The anticoagulant activity of UFH depends on both theumber of heparin molecules with the pentasaccharidehain in its composition and the size of molecules containinghe pentasaccharide. The high molecular weight heparinsill catalyze the inhibition of Xa and IIa factors, while

he low molecular weight heparins will only inhibit the Xaactor.58,59

Intravenous administration of UFH results in immediatenticoagulation, while subcutaneous administration resultsn onset of action within 1-2 hours. The anticoagulant effects both molecular weight and dose dependent, in a nonlin-ar manner, and increases disproportionately with increasedose.6 The biological half-life of heparin increases from0 minutes with 25 UI.kg-1 IV to 60 minutes with 100 UI.kg-1

nd to 150 minutes with 400 UI.kg-1.59

When given in therapeutic doses, UFH anticoagulations monitored by the activated partial thromboplastin timeaPTT). During cardiopulmonary bypass, coagulation inhibi-ion by high doses of heparin is monitored by the activatedlotting time (ACT). Subcutaneous administration of smalloses (5,000 IU) for prophylaxis of deep venous thrombo-is (DVT) usually does not change the aPTT. One of thedvantages of heparin anticoagulation is the reversal by pro-amine. Each milligram of protamine can neutralize 100 IUf heparin.58

A review study of more than 9,000 patients undergo-ng neuraxial block with prophylactic doses for DVT witheparin showed no cases of spinal hematoma.60 However,solated cases have been reported subsequently to thatevision.9,16,10,61---63 In patients receiving two- daily doseegimen of subcutaneous UFH (5,000 IU) there is no con-raindication for the use of neuraxial techniques.6 However,here are insufficient data to confirm the safety of neurax-al techniques with three daily doses, despite being the mostffective dosage for DVT prevention.64

In contrast to UFH prophylactic regimen, anticoagulationherapy is definitely associated with increased risk of spinalematoma4. A prospective study (n = 342) comparing thencidence of spinal hematoma in patients with and withoutherapeutic doses of UFH and undergoing lumbar puncture

howed incidence of 2% in the UFH group. The risk factorsere: (i) less than 1 hour interval between the onset of hep-rin and lumbar puncture; (ii) concomitant use of ASA at theime of lumbar puncture; and (iii) traumatic procedure.14

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ecently, two cases of epidural hematoma were reportedssociated with UFH therapy and neuraxial block.65,66

Heparinization during surgery involves the use of 5,000o 10,000 U of heparin intravenously during surgery, par-icularly in vascular surgery to prevent thrombosis duringrtery clamping.59 Most published cases series uses theame guidelines for neuraxial anesthesia management inhese patients, based on the exclusion of high-risk patientspreexisting coagulopathy) and performing the neuraxialechnique at least one hour before heparin administration.60

tafford-Smith showed increased incidence of bleedingn patients on ASA associated with intraoperative intra-enous heparin. SEH risk increased to 1:8,500 after epiduraluncture and to 1:12,000 after spinal anesthesia, evenhen neuraxial anesthesia and subsequent heparinizationccurred after one-hour interval.35

In cardiac surgery, the benefits of thoracic epidural anes-hesia on pulmonary function and analgesia are evident,ith lower intensity for arrhythmia management and noffect on hospital and ICU length of stay and mortality.67,68

owever, the benefits must be evaluated concerning theigh risk of SEH. The probability of spinal hematoma inatients undergoing cardiac surgery with full hepariniza-ion is 1:1,528 with epidural and 1:3,610 with spinalechniques.69,70 Experts recommend that neuraxial block beerformed the day before surgery due to complete surgicaleparinization.22,71,72 Because neuraxial blockade in cardiacurgery carries significant risks without improving morbiditynd mortality, there is discussion whether epidural or spinalnesthesia is justified, probably with the contraindication ofhe technique in this group.72

ecommendations

. In patients on two daily prophylactic doses of UFH (5,000IU) there are no contraindications to neuraxial block (D);6

. The safety of neuraxial block in patients receiving pro-phylactic doses of UFH above 10,000 IU or above twodaily doses is not established. Although dosage of threedaily doses may lead to increased surgical bleeding, itis unclear whether there is an increased risk for spinalhematoma development (D);6

. Because heparin-induced thrombocytopenia (HIT) mayoccur during UFH administration, platelet count shouldbe done before neuraxial technique or catheter removal,if the patient is on HNF for five or more days (B);3

. Wait a minimum interval of 4 hours between the last pro-phylactic dose of UFH and spinal/epidural puncture orepidural catheter removal. The next dose of prophylac-tic UFH should be administered at least one hour afterneuraxial anesthesia or epidural catheter removal (D);3

. If UFH is used in therapeutic doses to perform neurax-ial anesthesia, administration of continuous intravenousheparin therapy should be discontinued for at least4 hours before puncture or catheter removal, and it isnecessary to check the return of normal coagulation bydetermining aPTT or ACT (D);3

. In situations of intraoperative heparinization, the follow-ing recommendations should be considered: 1) minimuminterval of one-hour between puncture or catheter place-ment and heparinization; 2) do not perform neuraxial

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N.M. Fonseca et al.

block in patients with coagulopathy or on anticoagu-lants; 3) wait 4 hours between the last dose and epiduralcatheter removal, preferably with laboratory coagula-tion tests; 4) after catheter removal, wait one hour forUFH dose application; 5) although the occurrence of diffi-cult puncture or blood output from puncture needle mayincrease the risk of spinal hematoma, there are no datato justify surgery cancellation (A).6

ow molecular weight heparin (LMWH)

MWH has become the treatment of choice for both preven-ion and treatment of DVT, due to the greater bioavailabilityalmost 100%) after subcutaneous administration, whichesults in higher anticoagulant effect without increasingleeding tendency and ease of use without the need forlood coagulation monitoring.2

Pharmacology of LMWH differs from UFH. The main dif-erences are the highest inhibitory activity against thea factor compared with thrombin (IIa), anticoagulantffect difficult monitoring (factor Xa levels), prolonged half-ife, and lack of complete reversibility with protamine.58

ith subcutaneous administration, peak plasma levels areeached in approximately 3-4 hours, and the half-life oflimination, with normal renal function, is within 4-

hours.73,74 However, the anti-factor Xa activity remainsonsiderable (50%) after 10-12 hours of administration. Ifreatinine clearance falls below 30 mL.min-1, the half-lifeoubles.74 Compared to UFH, the risk of thrombocytopeniaHIT) is 10 times lower. However, they are contraindicatedn HIT due to the high risk of cross-reaction, approximately0%.75

If thromboprophylaxis with LMWH is prescribed in twoaily doses (30 mg), compared to a daily dose regimen, theisk of spinal hematoma may be increased, as the minimumevels of anti-Xa activity are higher.76

The use of LMWH in patients undergoing neuraxial blockas adopted in Europe in 1987. Dosages used were 20-40 mg

n a single dose 12 hours before surgery. To prevent theccurrence of spinal hematoma, guidelines recommendednsertion/removal of epidural catheter at a minimum inter-al of 10-12 hours after the last dose of LMWH. Theubsequent dose was restarted after 8-12 hours.5,16 Thus,eviews involving data from millions of patients showed thathe use of neuraxial block in subjects on LMWH under theuropean regime was safe, with report of only one case ofpinal hematoma.77,78

On the other hand, in the United States, enoxaparinntroduced in 1993 had no recommendation regarding timeetween drug administration and neuraxial block or catheteremoval. Enoxaparin was routinely administered in themmediate postoperative period at a dose of 30 mg twiceaily. After five years of use, the Food and Drug Administra-ion (FDA) accumulated reports of 43 patients undergoingeuraxial blocks who developed spinal hematoma.79 In 1998,3 cases of spinal hematoma associated with LMWH had beeneported in Europe, while in United States, it reached 60

ases.24 Reasons for the high rates were attributed to: (i)igher daily dose prescription of LMWH; (ii) more frequentoses, possibly leading to higher minimum blood level duringatheter insertion/removal; (iii) lack of practical guidelines

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for neuraxial block and LMWH administration; (iv) lack oflarger series.19,24

After the Second American Society of Regional Anesthesia(ASRA) resolution in 2003, studies in the English literaturereported 10 cases related to the combination of LMWH andspinal hematoma. Five additional cases were reported by theRoyal College of Anesthetists Consensus in the UK in 97,925epidural blocks, but without proven evidence of associationwith anticoagulant drugs.12

Recommendations

1. Antiplatelet drugs and oral anticoagulants concomitantlyadministered with LMWH increase the risk of spinalhematoma, and in such conditions blockade is contraindi-cated. In patients on ASA, it seems prudent to administerthe thromboprophylatic dose of heparin postoperatively(B).36 In these patients, if LMWH is administered preop-eratively, wait 24 hours to perform blockade or catheterremoval due to increased risk of bleeding (C);6

2. Bleeding during needle or catheter insertion does not jus-tify surgery cancellation. The beginning of therapy withLMWH in this circumstance should occur 24 hours afterthe end of surgery (D);6

3. In preoperative patients receiving LMWH thrombopro-phylaxis, neuraxial block is recommended 10-12 hoursafter the last dose of LMWH (D);6

4. In patients on therapeutic doses of LMWH, such as enoxa-parin 1 mg.kg-1 every 12 hours, enoxaparin 1.5 mg.kg-1

per day, dalteparin 120 IU.kg-1 every 12 hours, dalteparin200 IU.kg-1 per day or tinzaparin 175 IU.kg-1 per day, aninterval of at least 24 hours is recommended between thelast dose and neuraxial block to ensure normal hemosta-sis (D);6

5. Patients under prophylactic regimen of LMWH every12 hours (enoxaparin 30 mg twice daily), one dose shouldbe omitted to enable a 24 hours interval before neuraxialblock or catheter removal (A);3

6. Regarding LMWH postoperative use, the first dose shouldbe administered 6-8 hours after surgery. A second dose ofLMWH should not be administered before 24 hours of thefirst dose. Thus, epidural catheter may be safely main-tained. However, epidural catheter removal should onlybe done after 10-12 hours of the last dose. The subse-quent dose of LMWH after catheter removal should beadministered after 2 hours. No drugs that alter hemosta-sis should be given due to the risk of additive effects(D);6

7. In patients under twice daily dosage regimen, there isgreater risk of spinal