Brazilian Journal of Cardiovascular Surgery 30.4

Page 1

30.4 JULY/AUGUST 2015

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY | REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

VOL. 30 Nยบ 4 JULY/AUGUST 2015


2 01 6

SB C V C CONGRESS OF THE BRAZILIAN SOCIETY OF

CARDIOVASCULAR

SURGERY

INNOVATION

New Horizons in Cardiovascular surgery

6th Symposium of Nursing in Cardiovascular Surgery 6th Symposium of Physiotherapy in Cardiovascular Surgery 5th Academic Conference on Cardiovascular Surgery 34th Brazilian Congress of Extracorporeal Circulation

April 7-9 2016 • • Fortaleza • Ceará • Brazil

www.sbccv.org.br

You have good reasons to participate COMMEMORATIVE EDITION

30 YEARS BJCVS/RBCCV Special programming during the Congress in reference to the history and importance of the BJCVS journal. Find more info on the website.

PARALLEL EXHIBITION In the parallel exhibition reputable brands will exposure news on the sector offering ample opportunity up to date.

FREE THEMES

PROGRAM

HANDS ON A teaching and learning strategy, which enables interaction between expert and surgeons who wish to master new technologies of proven effectiveness. Membership success and positive feed back update in practical class.

Through lectures, round tables and advanced courses we will discuss, debate and share experiences on innovation and new horizons in cardiovascular surgery. As usual, the Congress brings together recognized experts of academic merit, highlighting national and international presences.

Medical Congress – there will be presentation of oral free themes in the official program distributed in prime time in parallel auditoriums. Symposia - there will be presentation of oral free themes and posters. Deadline for submission: October 1-15 November, 2015

Ensure your presence at BSCVS 2016 Congress Make your Registration PROMOTION Brazilian Society of Cardiovascular Surgery

ORGANIZATION

+55 (51) 3061-2959

OFFICIAL AGENCY

+55 (21) 2142.9315 sbccv2016@blumar.com.br




BJCVS

EDITOR-IN-CHIEF Prof. Dr. Domingo M. Braile - PhD

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

São José do Rio Preto - SP - Brasil domingo@braile.com.br

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

FORMER EDITORS • Prof. Dr. Adib D. Jatene • Prof. Dr. Fábio B. Jatene

EXECUTIVE EDITOR Ricardo Brandau - Postgraduate in Science Journalism S. José do Rio Preto (BRA) brandau@sbccv.org.br

EDITORIAL ASSISTANTS • Camila Safadi - Postgraduate in Project Management - PMI S. José do Rio Preto (BRA) - camila@sbccv.org.br • Rosangela Monteiro - PhD São Paulo (BRA) - rosangela.monteiro@incor.usp.br

PhD - São Paulo (BRA) [1986-1996] PhD - São Paulo (BRA) [1996-2002]

ASSOCIATE EDITORS • Antônio Sérgio Martins • Gilberto Venossi Barbosa • José Dario Frota Filho • José Teles de Mendonça • Luciano Cabral Albuquerque • Luis Alberto Oliveira Dallan • Luiz Felipe Pinho Moreira

Botucatu (BRA) Porto Alegre (BRA) Porto Alegre (BRA) Aracaju (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA)

• Manuel de Jesus Antunes • Mario O. Vrandecic Peredo • Michel Pompeu B. Oliveira Sá • Paulo Roberto Slud Brofman • Ricardo C. Lima • Ulisses A. Croti • Walter José Gomes

Coimbra (POR) Nova Lima (BRA) Recife (BRA) Curitiba (BRA) Recife (BRA) S.J. Rio Preto (BRA) São Paulo (BRA)

STATISTICS EDITOR • Orlando Petrucci Jr.

Campinas (BRA)

EDITORIAL BOARD • Adolfo Leirner • Adolfo Saadia • Alan H. Menkis • Alexandre Visconti Brick • Antônio Carlos G. Penna Jr. • Bayard Gontijo Filho • Borut Gersak • Carlos Roberto Moraes • Christian Schreiber • Cláudio Azevedo Salles • Djair Brindeiro Filho • Eduardo Keller Saadi • Eduardo Sérgio Bastos • Enio Buffolo • Fábio Biscegli Jatene • Fernando Antônio Lucchese • Gianni D. Angelini • Gilles D. Dreyfus • Ivo A. Nesralla • Jarbas J. Dinkhuysen • José Antônio F. Ramires • José Ernesto Succi • José Pedro da Silva • Joseph A. Dearani

São Paulo (BRA) Buenos Aires (ARG) Winnipeg (CAN) Brasília (BRA) Marília (BRA) Belo Horizonte (BRA) Ljubljana (SLO) Recife (BRA) Munich (GER) Belo Horizonte (BRA) Recife (BRA) Porto Alegre (BRA) Rio de Janeiro (BRA) São Paulo (BRA) São Paulo (BRA) Porto Alegre (BRA) Bristol (UK) Harefield (UK) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Rochester (USA)

ENGLISH VERSION • Fernando Pires Buosi • Marcelo Almeida

• Maria Carolina Zuppardo

GRAPHIC DESIGN AND LAYOUT • Heber Janes Ferreira

• Joseph S. Coselli • Luiz Carlos Bento de Souza • Luiz Fernando Kubrusly • Mauro Paes Leme de Sá • Miguel Barbero Marcial • Milton Ary Meier • Nilzo A. Mendes Ribeiro • Noedir A. G. Stolf • Olivio Alves Souza Neto • Otoni Moreira Gomes • Pablo M. A. Pomerantzeff • Paulo Manuel Pêgo Fernandes • Paulo P. Paulista • Paulo Roberto B. Évora • Pirooz Eghtesady • Protásio Lemos da Luz • Reinaldo Wilson Vieira • Renato Abdala Karam Kalil • Renato Samy Assad • Roberto Costa • Rodolfo Neirotti • Rui M. S. Almeida • Sérgio Almeida de Oliveira • Tomas A. Salerno

Houston (USA) São Paulo (BRA) Curitiba (BRA) Rio de Janeiro (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Salvador (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Belo Horizonte (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Ribeirão Preto (BRA) Cincinatti (USA) São Paulo (BRA) Campinas (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) Cambridge (USA) Cascavel (BRA) São Paulo (BRA) Miami (USA)

OFFICIAL ORGAN OF THE BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY SINCE 1986


ADDRESS/ENDEREÇO

Brazilian Society of Cardiovascular Surgery Sociedade Brasileira de Cirurgia Cardiovascular

Rua Afonso Celso, 1178 • Vila Mariana • Phone: 55 11 3849-0341. Fax: 55 11 5096-0079. Zip code: 04119-061 • São Paulo, SP, Brazil E-mail BJCVS/RBCCV: revista@sbccv.org.br • E-mail SBCCV: sbccv@sbccv.org.br • Site SBCCV: www.sbccv.org.br • Sites BJCVS/RBCCV: www.scielo.br/rbccv/www.rbccv.org.br/www.bjcvs.org (also for article submission)

Bimonthly publication/Publicação bimestral Print edition - Print run: 250 copies

(*)

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR (Sociedade Brasileira de Cirurgia Cardiovascular) São Paulo, SP - Brasil. v. 119861986, 1: 1,2 1987, 2: 1,2,3 1988, 3: 1,2,3 1989, 4: 1,2,3 1990, 5: 1,2,3 1991, 6: 1,2,3 1992, 7: 1,2,3,4 1993, 8: 1,2,3,4 1994, 9: 1,2,3,4 1995, 10: 1,2,3,4 1996, 11: 1,2,3,4

1997, 12: 1,2,3,4 1998, 13: 1,2,3,4 1999, 14: 1,2,3,4 2000, 15: 1,2,3,4 2001, 16: 1,2,3,4 2002, 17: 1,2,3,4 2003, 18: 1,2,3,4 2004, 19: 1,2,3,4 2005, 20: 1,2,3,4 2006, 21: 1 [supl] 2006, 21: 1,2,3,4

2007, 22: 1 [supl] 2007, 22: 1,2,3,4 2008, 23: 1 [supl] 2008, 23: 1,2,3,4 2009, 24: 1 [supl] 2009, 24: 1,2,3,4 2009, 24: 2 [supl] 2010, 25: 1,2,3,4 2010, 25: 1 [supl] 2011, 26: 1,2,3,4 2011, 26: 1 [supl]

ISSN 1678-9741 - On-line version. ISSN 0102-7638 - Print version RBCCV 44205

2012, 27: 1,2,3,4 2012, 27: 1 [supl] 2013, 28: 1,2,3,4 2013, 28: 1 [supl] 2014, 29: 1,2,3,4 2014, 29: 1 [supl] 2015, 30: 1,2,3,4 2015, 30: 2 [supl]

CDD 617.4105 NLM18 WG 168

(*) ASSOCIAÇÃO PAULISTA DE BIBLIOTECÁRIOS. Grupo de Bibliotecários Biomédicos. Normas para catalogação de publicações seriadas nas bibliotecas especializadas. São Paulo, Ed. Polígono, 1972

INDEXED IN • Thomson Scientific (ISI) http://science.thomsonreuters.com • PubMed Central www.ncbi.nlm.nih.gov/pmc/

• LATINDEX - Sistema Regional de Información en Línea para Revistas Cientificas de America Latina, el Caribe, España y Portugal www.latindex.unam.mx

• PubMed/Medline www.ncbi.nlm.nih.gov/sites/entrez

• Index Copernicus www.indexcopernicus.com

• SciELO - Scientific Library Online www.scielo.br

• Google scholar http://scholar.google.com.br/scholar

• Scopus www.info.scopus.com

• EBSCO www2.ebsco.com/pt-br

• LILACS - Literatura Latino-Americana e do Caribe em Ciências da Saúde. www.bireme.org


BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR DEPARTMENT OF SURGERY OF THE BRAZILIAN SOCIETY OF CARDIOLOGY DEPARTAMENTO DE CIRURGIA DA SOCIEDADE BRASILEIRA DE CARDIOLOGIA

“Enhancing the professional on behalf of the patient” BOARD OF DIRECTORS 2014 - 2015 President: Vice-President: Secretary General: Treasurer: Scientific Director:

Marcelo Matos Cascudo (RN) Fábio Biscegli Jatene (SP) Henrique Murad (RJ) Eduardo Augusto Victor Rocha (MG) Rui M.S. Almeida (PR)

Advisory Board:

Bruno Botelho Pinheiro (GO) Henrique Barsanulfo Furtado (TO) José Pedro da Silva (SP) Luciano Cabral Albuquerque (RS) Ricardo de Carvalho Lima (PE)

Journal Editor: Site Editor: Newsletter Editors:

Domingo Marcolino Braile (SP) João Carlos Ferreira Leal (SP) Walter José Gomes (SP) Domingo Marcolino Braile (SP) Orlando Petrucci (SP) Luciano Cabral Albuquerque (RS) Fernando Ribeiro Moraes Neto (PE)

Presidents of Regional Afilliates Norte-Nordeste: Rio de Janeiro: São Paulo: Minas Gerais: Centro-Oeste: Rio Grande do Sul: Paraná: Santa Catarina:

Vinícius José da Silva Nina (MA) Marcelo Sávio da Silva Martins Rubens Tofano de Barros Rodrigo de Castro Bernardes Jorge Luiz França de Vasconcelos (MS) Marcela da Cunha Sales Luiz César Guarita Souza Milton de Miranda Santoro

Departments DCCVPED: DECAM: DECA: DECEM: DEPEX: DECARDIO: DBLACCV: ABRECCV:

Luiz Fernando Canêo (SP) Juan Alberto Cosquillo Mejia (CE) Cláudio José Fuganti (PR) Eduardo Keller Saadi (RS) Alexandre Ciappina Hueb (SP) José Carlos Dorsa V. Pontes (MS) Leila Nogueira Barros (SP) Paulo Marcelo Barbosa Mesquita (SP)


BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR E-mail: revista@sbccv.org.br Websites: www.scielo.br/rbccv www.bjcvs.org


BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

ISSN 1678-9741 - On-line ISSN 0102-7638 - Print RBCCV 44205

Impact Factor: 0.550

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR Braz J Cardiovasc Surg/Rev Bras Cir Cardiovasc, (São José do Rio Preto, SP - Brazil) jul/aug - 2015;30(4):409-514

CONTENTS EDITORIALS

The scientific article and the good science O artigo científico e a boa ciência Domingo M. Braile.................................................................................................................................................................................. I

There is one more thing to be done: ECMO! Há algo mais a ser feito: ECMO! Fernando Antoniali................................................................................................................................................................................ IV

ORIGINAL ARTICLES 1658 Post-cardiotomy ECMO in pediatric and congenital heart surgery: impact of team training and equipment in the results ECMO pós-cardiotomia em cirurgia cardíaca pediátrica e congênita: impacto do treinamento da equipe e equipamentos nos resultados Leonardo Augusto Miana, Luiz Fernando Canêo, Carla Tanamati, Juliano Gomes Penha, Vanessa Alves Guimarães, Nana Miura, Filomena Regina Barbosa Gomes Galas, Marcelo Biscegli Jatene.....................................................................................................409 1659 Oxidative stress in coronary artery bypass surgery Estresse oxidativo na cirurgia de revascularização miocárdica Amaury Edgardo Mont'Serrat Ávila Souza Dias, Petr Melnikov, Lourdes Zélia Zanoni Cônsolo......................................................417 1660 Transcatheter aortic valve implantation with balloon-expandable valve: early experience from China Implantação da válvula aórtica transcateter com válvula balão-expansível: experiência inicial da China Qingsheng Lu, Yifei Pei, Hong Wu, Zhinong Wang, Jing Zaiping......................................................................................................425 1661 Comparison of two technics of cardiopulmonary bypass (conventional and mini CPB) in the trans- and postoperative periods of cardiac surgery Comparação de duas técnicas de circulação extracorpórea (convencional e mini CEC), nos períodos trans e pós-operatório de cirurgia cardíaca Sergio Nunes Pereira, Izabelle Balta Zumba, Micheline Sulzbacher Batista, Daniela Da Pieve, Elisandra dos Santos, Ralf Stuermer, Gerson Pereira de Oliveira, Roberta Senger........................................................................................................................................433 1662 Relationship between pre-extubation positive end-expiratory pressure and oxygenation after coronary artery bypass grafting Relação entre a pressão expiratória positiva final pré-extubação e a oxigenação após revascularização cirúrgica do miocárdio Reijane Oliveira Lima, Daniel Lago Borges, Marina de Albuquerque Gonçalves Costa, Thiago Eduardo Pereira Baldez, Mayara Gabrielle Barbosa e Silva, Felipe André Silva Sousa, Milena de Oliveira Soares, Jivago Gentil Moreira Pinto................................443 1663 Evaluation of the influence of pulmonary hypertension in ultra-fast-track anesthesia technique in adult patients undergoing cardiac surgery Avaliação da influência da hipertensão pulmonar na técnica anestésica ultra-fast-track em pacientes adultos submetidos à cirurgia cardíaca Paulo Sérgio da Silva, Márcio Portugal Trindade Cartacho, Casimiro Cardoso de Castro, Marcello Fonseca Salgado Filho, Antônio Carlos Aguiar Brandão.........................................................................................................................................................................449 1664 Effects of intraoperative diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery Efeitos da infusão intraoperatória de diltiazem sobre as mudanças do fluxo em enxertos arteriais e venosos em cirurgia de revascularização do miocárdio Ozan Erdem, Mehmet Erdem Memetoğlu, Ali İhsan Tekin, Ümit Arslan, Özgür Akkaya, Rasim Kutlu, İlhan Gölbaşı....................459 1665 Effect of using pump on postoperative pleural effusion in the patients that underwent CABG Efeito da circulação extracorpórea no derrame pleural pós-operatório em pacientes submetidos à revascularização do miocárdio Mehmet Özülkü, Fatih Aygün..............................................................................................................................................................466


1666 Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program Treinamento muscular inspiratório de curto prazo potencializa os benefícios do treinamento aeróbico e resistido em pacientes após CRM na fase II de programa de reabilitação cardíaca Bárbara Maria Hermes, Dannuey Machado Cardoso, Tiago José Nardi Gomes, Tamires Daros dos Santos, Marília Severo Vicente, Sérgio Nunes Pereira, Viviane Acunha Barbosa, Isabella Martins de Albuquerque............................................................................474 1667 Cardiopulmonary bypass increases the risk of vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure O uso da circulação extracorpórea aumenta o risco de síndrome vasoplégica em pacientes com insuficiência renal crônica hemodialítica submetidos à revascularização cirúrgica do miocárdio Nelson Américo Hossne Junior, Matheus Miranda, Marcus Rodrigo Monteiro, João Nelson Rodrigues Branco, Guilherme Flora Vargas, José Osmar Medina de Abreu Pestana, Walter José Gomes.................................................................................................................482 REVIEW ARTICLE 1668 Sternal wound tuberculosis following cardiac operations: a review Tuberculose na ferida esternal após operações cardíacas: uma revisão Shi-Min Yuan.......................................................................................................................................................................................489 BRIEF COMMUNICATION 1669 Aortic rupture during reoperative bariatric surgery Ruptura da aorta durante a cirurgia bariátrica Sorin Hostiuc, Constantin Dragoteanu, Victor Asavei, Ionut Negoi....................................................................................................494 HOW-TO-DO-IT 1670 Off-pump bidirectional Glenn through right anterior thoracotomy Glenn bidirecional sem uso de CEC via toracotomia anterior direita Maximo Guida, Andrea Lo Cascio, Gustavo Guida, Gabriel Guida, Estefania De Garate, Manuel Vasquez, Fernando Prieto, Miriam Pecchinenda..........................................................................................................................................................................................497 CLINICAL-SURGICAL CORRELATION 1671 Pediculated myxoma from atrial septum invading atria and biventricular inlets Mixoma pediculado do septo interatrial invadindo átrios e vias de entradas biventriculares Camila Caetano Cardoso, Ulisses Alexandre Croti, Carlos Henrique De Marchi, Airton Camacho Moscardini................................501 LETTERS TO THE EDITOR 1672 Relationship between pre-extubation positive end-expiratory pressure and oxygenation after coronary artery bypass grafting Marcos Aurélio Barboza de Oliveira, Antonio Carlos Brandi, Carlos Alberto dos Santos, Paulo Henrique Husseini Botelho...............504 1673 Key points of reducing neurologic complications in frozen elephant trunk technique Murat Kadan, Gokhan Erol, Kubilay Karabacak, Mevlüt Kobuk........................................................................................................505 1674 Answer to “Key points of reducing neurologic complications in frozen elephant trunk technique” Ricardo Ribeiro Dias, Jose Augusto Duncan.......................................................................................................................................506 Reviewers BJCVS 30.4.......................................................................................................................................................................507 Instructions for authors.....................................................................................................................................................................508 Meetings Calendar.............................................................................................................................................................................513 Printed in Brazil


Editorial

The scientific article and the good science O artigo científico e a boa ciência

Domingo M. Braile1 DOI: 10.5935/1678-9741.20150064

T

he scientific paper is one of the most visible areas of science. It is disseminating his ideas, new techniques and discoveries that the scientist, whether he is doctor, physician, biologist, engineer etc., plays his role in the expansion of knowledge and the consequent benefit to society and may break paradigms. This process is not simple, as we know, going through a series of bottlenecks ranging from consulting the relevant literature, research, data compilation, writing, journal’s choice, where it passes through the sieve of the reviewers, final approval by the Editor and finally adjustments, in minor or major ways, until its release/publication. Currently, the requirements are higher, either because postgraduate school to which the author is connected requires publishing studies in journals with higher impact factor (IF), depending on the CAPES criteria (Qualis Capes)[1], in the case of Brazil, or the need for the article is written in English so it can be read, and eventually cited by the greatest number of readers. In choosing a journal until the speed of dissemination of knowledge on the Internet, it is important, since today’s novelty turns into something “outdated” tomorrow. Aware of this new scenario, scientific journals have sought to refine their acceptance criteria and publishing articles. The Scielo has encouraged the journals that are part of its regular basis to take action accordingly. This creates a side effect, which is the increasing rejection of studies, either in submission or during the review process. In journals from various fields, not only among the best known, the rate of rejected manuscripts exceeds 90%[2]. In The Lancet, for example, it is 95%[3]. In journals restricted to a specific area such as the Brazilian Journal of Cardiovascular Surgery (BJCVS), the percentage is somewhat lower, but has been increasing over the years. The BJCVS, aware that despite the new additions in recent years it still has a long way to go, has not measured efforts to walk “pari passu” with the best-known journals. Our rejection rate is rising gradually. In 2013, of 186 studies received, 61 were rejected (32.79%). In 2014, we received 162 manuscripts and 70 were rejected (43.21%). The average time between the submission of the study and the decision to approve or reject fell 147 days in 2013 to 86 days in the last year (Table 1).

This shows our commitment to rigor and good science. Reviewers, also Brazilians overwhelmingly (Table 2), have been instructed to be strict and in some cases the study, when it is appropriate and does not have methodological errors, can incorporate adaptations suggested by the editor and reviewers, to be formatted according to the journal’s standards and stand ready to be published in hard copy and/or electronic form. Table 1. Number of manuscripts received, approved and rejected by the Brazilian Journal of Cardiovascular Surgery in 2013 and 2014* Item

1 2 3 4

Total 2014 Articles Sent 162 Articles Approved 65 Articles Refused 70 Time between submission and approval (days) 96

Total 2013 186 104 61 147

* The difference between the total number and sum of approved and disapproved articles justified by the fact that not all articles received in a given year are published in the same year of submission, as in the case in question. Source: GN1 Sistemas e Publicações.

Table 2. Countries of origin of authors and reviewers of manuscripts submitted to Brazilian Journal of Cardiovascular Surgery in 2013 and 2014. Country

1 2 3 4 5 6 7 8 9 10 11

Authors Authors Reviewers Reviewers 2014 2013 2014 2013 Brazil 104 139 120 123 Turkey 9 12 0 0 China 6 4 0 0 Colombia 2 1 0 0 Portugal 1 0 1 1 Germany 1 0 0 0 Greece 1 2 0 0 0 Italy 1 0 0 0 Serbia and Montenegro 1 0 0 Venezuela 1 0 0 0 United States 0 2 2 2

Source: GN1 Sistemas e Publicações.

I

Braz J Cardiovasc Surg | Rev Bras Cir Cardiovasc


Seeking the rapid spread of the item after the approval, pending the publication of a new issue of the journal the manuscript is available “ahead of print” already with the DOI (Digital Object Identifier) allowing its citation in the literature. Despite all our efforts to internationalize the BJCVS, it is still an eminently Brazilian journal. In 2013, of the total number of items received, 161 were from Brazil, followed by 14 from Turkey, 4 from China, 2 from the United States, 2 from Greece, 1 from Argentina, 1 from Colombia and 1 from the Netherlands. In 2014, 120 were from Brazil, 22 from China, 11 from Turkey, 2 from Colombia, 2 from Greece and 1 from Germany, 1 from Italy, 1 from Portugal, 1 from Serbia and 1 from Venezuela (Table 3). Due to the largest number of studies received, Brazil was the country with the largest number of rejected manuscripts (Table 4). With the adoption of English as the official language of the journal, six issues a year and a greater increase in disclosure, we hope to receive more international quality studies, and also from Brazil.

Without being redundant, I explain the reason to emphasize that the studies should be of quality and international. I see this as the only way to see our IF increase because the chance of readers of BJCVS to cite our journal in other publications that also are in the Thomson database and the Scopus increases in parallel to these parameters. Redalyc Aiming to expand our visibility, after various requirements and a long time in another database, the Redalyc admitted us (http://www.redalyc.org/). Based in Mexico, Redalyc has nearly 1,000 open access journals, allowing the dissemination of scientific information. 30 years As we reported in previous editions, we are preparing, together with the Board of the Brazilian Society of Cardiovascular Surgery (BSCVS), several activities to commemorate the 30th anniversary of the BJCVS. In programming of the 43rd Brazilian Congress of Cardiovascular Surgery, which will take place from 7 to 9 April 2016, in Fortaleza, there will be a module in the programming dedicated to our journal, where we discuss topics of interests of authors, reviewers and professionals of health field in general, who are interested in scientific production. We will also pay tribute to our partners, who over these nearly three decades spared no efforts so that the BJCVS could be what it is today. We trust that even facing many obstacles, never interrupting the circulation, the perspective is positive for us to continue our successful track record. The journal is available on multiple platforms, is present in social networks and always attentive to new technology and, of course, always trying to improve its content.

Table 3. Countries of origin of the manuscripts submitted to Brazilian Journal of Cardiovascular Surgery in 2013 and 2014. Country Brazil China Turkey Colombia Greece Germany Italy Portugal Serbia and Montenegro Venezuela Argentina Netherlands United States

1 2 3 4 5 6 7 8 9 10 11 12 13

2014 120 22 11 2 2 1 1 1 1 1 0 0 0

2013 161 4 14 1 2 0 0 0 0 0 1 1 2

CME The following items are available for the testing of Continuing Medical Education (CME) in this issue: “Post-cardiotomy ECMO in pediatric and congenital heart surgery: impact of team training and equipment in the results” (page 409); “Relationship between pre-extubation positive end-expiratory pressure and oxygenation

Source: GN1 Sistemas e Publicações.

Table 4. Countries of origin of the manuscripts rejected by the Brazilian Journal of Cardiovascular Surgery in 2013 and 2014. 1 2 3 4 5 6 7 8

Country Brazil Turkey China Germany Argentina Colombia Greece Netherlands

Without Referee 2014 25 5 4 1 0 0 0 0

With Referee 2014 27 0 7 0 0 1 0 0

Without Referee 2013 18 4 1 0 0 0 1 0

Source: GN1 Sistemas e Publicações.

II

Braz J Cardiovasc Surg | Rev Bras Cir Cardiovasc

With Referee 2013 31 2 2 0 1 0 0 1


after coronary artery bypass grafting” (page 443); “Evaluation of the influence of pulmonary hypertension in ultra-fast-track anesthesia technique in adult patients undergoing cardiac surgery” (page 449); “Effects of intraoperative diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery” (page 459). I emphasize that the CME is a valuable tool for learning and updating of knowledge and is worth 0.5 points in the BJSVC proof of title. We are open to suggestions and criticisms to improve the system.

REFERENCES

1. Brasil. Ministério da Educação. Fundação CAPES. Classificação da Produção Intelectual [Cited 2015 Aug 18]. Available from: http://www.capes.gov.br/avaliacao/instrumentos-de-apoio/ classificacao-da-producao-intelectual 2. American Psychological Association. Journals Statistics and Operation Data. 2013 Statistics [Cited 2015 Aug 1]. Available from: http://www.apa.org/pubs/journals/features/2013statistics.pdf

My warmest regards,

3. The Lancet. How The Lancet handles your paper [Cited 2015 Aug14]. Available from: http://www.thelancet.com/lancetinformation-for-authors/how-the-lancet-handles-your-paper

Domingo Braile 1 Editor-in-Chief - BJCVS/RBCCV

III

Braz J Cardiovasc Surg | Rev Bras Cir Cardiovasc


Editorial

There is one more thing to be done: ECMO! Há algo mais a ser feito: ECMO!

Fernando Antoniali1

DOI: 10.5935/1678-9741.20150066

“ – Unfortunately, it is not possible to get out of cardiopulmonary bypass. We have already tried several times and it is not working. We will have to let the patient die! I will talk to the family…” This is an extremely distressing situation for all the team involved in a cardiac surgery. Everyone who has been present in a moment like this and have the humility to recognize certainly will not deny how difficult it is to make the decision: turn off the pump and allow the patient to die. Especially, if the surgery is going on for several hours and there were many attempts to wean from cardiopulmonary bypass (CPB). Especially, if the patient is a child and the parents are outside waiting anxiously for a successful surgical repair. However, for the most part of these patients, we can say that there is one more thing to be done. We cannot use this claim for all the patients with cardiac and respiratory failure after a heart surgery but for the most part of them, we can! For sure! Despite some of these patients can get out of the operating room with high doses of vasoactive drugs or high parameters of mechanical ventilation, the circulatory failure and severe hypoxia will culminate with important acidosis, multiple organ failure and the patient will die a few days later. The post-cardiotomy ECMO (Extracorporeal Membrane Oxygenation) is the best option to support these patients. Nevertheless, it is necessary to use a real post-cardiotomy ECMO because keeping the patient on CPB in the ICU will not work. If we are talking about ECMO, the numbers from the ELSO registry (Extracorporeal Life Support Organization) must be highlighted. The last ELSO international report was on July 2015 and there were 69.114 ECMO patients in the registry with an overall survival of 59%[1]. Inside of this big group of patients, 10.183 cases were neonates and infants under 16 years old with congenital heart problems and they were supported with a cardiac ECMO. The majority of them received

the support because of cardiac failure after CPB or during the first postoperative day. In this post-cardiotomy ECMO group, the mean survival was 42.7%. Using these information from ELSO, at least we should say that it is mandatory remember about ECMO as a possibility of treatment for a patient with cardiac failure after CPB. However, it is not a widespread knowledge in our country and some people don’t understand it. There is no doubt that the treatment with ECMO is increasing in Brazil but we still have to expand the information about it and improve the quality of this therapeutic technique in our country. Another important action would be the incorporation of this technology on the treatment of our patients from the public health system (SUS). In order to spread information about ECMO, the First Latin American ELSO Conference was performed in Brazil on December 2014. There were over 500 health professionals present with the majority of Brazilians and this event was the first scientific meeting of the Latin American chapter of ELSO that was created in 2012 following examples as the Euro ELSO and Asian-Pacific ELSO. The registrants discussed different issues about cardiopulmonary support with more than 20 international speakers, including Dr. Robert Bartlett, called “The Father of ECMO” who, on the opening ceremony, talked about the experimental studies of his group in the 1960’s and also about the first ECMO survival patients in the 1970’s. Fortunately, ECMO is not an experimental therapy anymore and the fact of more than 69 thousands of patients had been treated until now can prove it.

READ ARTICLE ON PAGE 409

The article “Post-cardiotomy ECMO in pediatric and congenital heart surgery: impact of team training and equipment in the results” published in this issue by Leonardo Miana and all the group of INCOR-SP (see page 409), demonstrated that 0.5% of the pediatric patients operated with the use of CPB needed ECMO because of cardiac or pulmonary failure. This

Coordinator of the Pediatric Cardiac Surgery at PUC-Campinas and the Cardio Surgical Clinic ECMO group of Campinas linked to ELSO, Campinas, SP, Brazil. E-mail: ferantoniali@uol.com.br 1

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information is in agreement with the numbers related for other groups, whose mention between 0.5 and 2% for adults and infants. Therefore it is not a rare situation and we need to pay attention. Everyone doing more than 10 patients a month probably will have a case to use post-cardiotomy ECMO. However, if there is no concern about the quality of this type of treatment, the survival rate will be very low and spending money, time and energy of the team, will not be worth. On a scenario when very few patients survive and go home, ECMO will be called as “Este Cliente Morreu Ontem” that means in English: “This patient died yesterday” - or even worse “Esta Criança Morreu Ontem”, when we are talking about pediatric patients: “This child died yesterday”. The INCOR-SP group points out the changes on the results after incorporating new materials and equipments and in special after staff training. The statistical difference between the survival rate of 5% before the new ECMO program and 45% nowadays is evident and confirms that it is the right way. The good news is that we already have in Brazil almost all the adequate materials and equipments to do ECMO in a high level. And so, we should worry with staff training. It is necessary a change of concepts! ECMO is not a treatment in which the responsible professionals are the cardiac surgeon and the perfusionist. The participation of the intensivists and the nursing staff is essential. In fact, the concept of an “ECMO specialist” is the ELSO proposal and it includes in the same group, the perfusionists, the nurses and even the respiratory therapists, which - after training - would have the ability to take care of the ECMO circuit and components, checking the quality of them, collecting samples for laboratory exams, administering volumes and drugs, changing parameters and even solving possible complications. This training program has to be done with classroom instructions and practical simulations, and must be repeated periodically because the number of cases can be small and the team has to be always prepared for the next one. The results also improved in Campinas-SP since we put in practice this “change of concepts” at the hospitals which our team – the Clínica Cardio Cirúrgica Campinas – is working. The participation of the intensive physicians and the nursing staff, taking care of the ECMO patients, makes that the maintenance of the medical management with ECMO becomes a group decision and not only a surgeon procedure. Specially, on the pediatric group, the information about a possible post-cardiotomy ECMO is previously communicated to the ICU team and it reduces the pressure on the surgical team. Moreover, as our team works in general hospitals, the good results with the ECMO support changed the mind of the ICU groups and nowadays we are having neonates, infants and adults patients, going on ECMO for exclusively respiratory problems. In conclusion, we can mention our results to strengthen the concept that training is the right way to go because our ECMO weaning rate has increased from 60% to 88.9% and our late survival, after hospital discharge, from 10% to 77.8% in the pediatric group (cardiac and respiratory patients)[2].

It is necessary an “ECMO team” with surgeons, intensivists and “ECMO specialists” working together in a reference center. In fact, ECMO must not be done at all hospitals in the country because it would increase the costs and certainly the results would be poor. However, the centers prepared for that must receive payment for all the staff involved 24 hours a day and for the materials and equipments used to keep the patients on ECMO support. The CESAR trial compared adults patients with ARDS treated with optimized mechanical ventilation in a group and on ECMO support in the other. The mortality (37% X 53%) and the costs were lower in the ECMO group. One important aspect of this UK study was that the patients on ECMO were treated in reference centers[3]. Before ending this editorial, I would like to talk about a wrong decision made by CONITEC – “Comissão Nacional de Incorporação de Tecnologias no SUS”. Recently, this committee didn’t approve the request to incorporate ECMO support for patients of our public health system (“Sistema Único de Saúde” - SUS)[4]. This request was made based in a detailed technical and scientific advice (“Parecer Técnico Científico” – PTC) which was extremely accepted in an open public consultation. Surprisingly, the CONITEC’s decision was in the opposite direction compared to what is happening in Brazil. The use of ECMO has increased and the results are improving mostly because of the training courses which are been offered in different parts of our country. After the First Latin American ELSO Conference, the number of Brazilians centers linked to ELSO, following the guidelines and reporting their numbers to the same registry, grew up from 3 to 9! In addition, there are others centers doing ECMO in Brazil and they intend to be part of ELSO too! Probably, very soon we will have more Brazilians scientific articles as the one published in this issue of BJCVS. Recently, Lima et al.[5] demonstrated the advantages with the ECMO support to save patients after Heart Transplants in Brasília – capital city of Brazil. Another interesting paper about the economic aspects of ECMO to adult patients with ARDS in Brazil, was written by Park et al.[6] and it informs that this technology is cost effective. And even though the number of Brazilians papers about ECMO is too small at this time – we can find just 25 in the MEDLINE with the terms “ECMO” and “Brazil” – there are over 8.000 international papers about ECMO in the same bibliographic database and less than 150 are experimental studies. And even more, among this huge number of scientific articles, 1.750 are reviews! There are many studies discussing the increasing rates of survival but if we look on the numbers of the last ELSO report, the survival rates for cardiac ECMO are 41%, 51% and 42% for neonates, pediatrics and adults, respectively and talking about respiratory ECMO the numbers are even better with 74%, 57% and 58% of survival for the same groups[1]. Changing these percentages for absolute numbers we have 38.616 patients that survived with ECMO. Therefore there is no reason to affirm that such a treatment

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which has saved more than 38 thousands of lives is not good for our public health system (SUS) patients! In conclusion, there are still some actions to be done regarding the use of ECMO in our country. We need to reverse the CONITEC decision. We need to have more ECMO support for patients with cardiopulmonary failure after CPB. We need to train people and we need to have reference centers which can receive patients to be ECMO supported with good results. We need to use ECMO to save more lives!

2. Antoniali F, Damiano AP, Oliveira JMVP, Silva JL, Santos V, Silva DB, et al. ECMO support for neonates and infants in general hospitals at Campinas-SP. Rev Bras Cir Cardiovasc. 2015;30(2 Suppl 1):49-101 (Abstract). 3. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al.; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomized controlled trial. Lancet. 2009;374(9698):1351-63.

Really, there is one more thing to be done: ECMO!

4. CONITEC. Relatório de Recomendação: Uso da Oxigenação Extracorpórea no Suporte de Pacientes com Insuficiência Respiratória. [cited 2015 Aug 21]. Avaliable from: http://conitec. gov.br/images/Relatorios/2015/Relatorio_ECMO_final.pdf

And so, we may use another approach for difficult situations that certainly we will need to face: “- Unfortunately, we are not doing a good job trying to wean from CPB. I prefer not to overdo it with high levels of vasoactive drugs and bad ventilation. We had already planned and everyone is advised. Let’s take the patient to the ICU on ECMO.”

5. Lima EB, Cunha CR, Barzilai VS, Ulhoa MB, Barros MR, Moraes CS, et al. Experience of ECMO in Primary Graft Dysfunction after Orthotopic Heart Transplantation. Arq Bras Cardiol. 2015 Jul 21. [epub ahead of print] 6. Park M, Mendes PV, Zampieri FG, Azevedo LC, Costa EL, Antoniali F, et al.; ERICC research group; ECMO group Hospital Sírio Libanês and Hospital das Clínicas de São Paulo. The economic effect of extracorporeal membrane oxygenation to support adults with severe respiratory failure in Brazil: a hypothetical analysis. Rev Bras Ter Intensiva. 2014;26(3):253-62.

REFERENCES

1. ELSO – Extracorporeal Life Support Organization: ECLS Registry Report. International Summary. July, 2015. [cited 2015 Aug 21]. Available from: https://www.elso.org/Registry/ Statistics/InternationalSummary.aspx

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Braz J Cardiovasc Surg 2015;30(4):409-16

Miana LA, et ORIGINAL al. - Post-cardiotomy ECMO in pediatric and congenital heart ARTICLE surgery: impact of team training and equipment in the results

Post-cardiotomy ECMO in pediatric and congenital heart surgery: impact of team training and equipment in the results ECMO pós-cardiotomia em cirurgia cardíaca pediátrica e congênita: impacto do treinamento da equipe e equipamentos nos resultados

Leonardo Augusto Miana1, MD, PhD; Luiz Fernando Canêo1, MD, PhD; Carla Tanamati1, MD, PhD; Juliano Gomes Penha1, MD; Vanessa Alves Guimarães1; Nana Miura1, MD, PhD; Filomena Regina Barbosa Gomes Galas1, MD, PhD; Marcelo Biscegli Jatene1, MD, MSc, PhD

DOI: 10.5935/1678-9741.20150053

RBCCV 44205-1658

Abstract Introduction: Post-cardiotomy myocardial dysfunction requiring mechanical circulatory support occurs in about 0.5% of cases. In our environment, the use of extracorporeal membrane oxygenation has been increasing in recent years. Objective: To evaluate the impact of investment in professional training and improvement of equipment in the rate of weaning from extracorporeal membrane oxygenation and survival. Methods: A retrospective study. Fifty-six pediatric and/or congenital heart patients underwent post-cardiotomy extracorporeal membrane oxygenation at our institution between November 1999 and July 2014. We divided this period into two phases: phase I, 36 cases (before the structuring of the extracorporeal membrane oxygenation program) and phase II, 20 cases (after the extracorporeal membrane oxygenation program implementation) with investment in training and equipment). Were considered as primary outcomes: extracorporeal membrane oxygenation weaning and survival to hospital discharge. The results in both phases were compared using Chi-square

test. To identify the impact of the different variables we used binary logistic regression analysis. Results: Groups were comparable. In phase I, 9 patients (25%) were weaned from extracorporeal membrane oxygenation, but only 2 (5.5%) were discharged. In phase II, extracorporeal membrane oxygenation was used in 20 patients, weaning was possible in 17 (85%), with 9 (45%) hospital discharges (P<0.01). When the impact of several variables on discharge and weaning of extracorporeal membrane oxygenation was analyzed, we observe that phase II was an independent predictor of better results (P<0.001) and need for left cavities drainage was associated with worse survival (P=0.045). Conclusion: The investment in professional training and improvement of equipment significantly increased extracorporeal membrane oxygenation results.

Heart Institute of the Clinics Hospital of the Medical School at University of São Paulo (InCor HC-FMUSP), São Paulo, SP, Brazil.

Correspondence Address: Leonardo Augusto Miana Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo Av. Dr. Enéas de Carvalho Aguiar, 44, Bloco 2, 2° Andar, sala 5 - Cerqueira Cesar - São Paulo, SP, Brazil Zip code: 05403-900 E-mail: leonardomiana@gmail.com

Descriptors: Extracorporeal Membrane Oxygenation. Evaluation of Results of Preventive Actions. Heart Defects, Congenital. Health Human Resource Training. Cardiovascular Surgical Procedures.

1

This study was carried out at Heart Institute of the Clinics Hospital of the Medical School at University of São Paulo (InCor HC-FMUSP), São Paulo, SP, Brazil.

Article received on March 6th, 2015 Article accepted on July 27th, 2015

No financial support.

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Miana LA, et al. - Post-cardiotomy ECMO in pediatric and congenital heart surgery: impact of team training and equipment in the results

estruturação do programa de ECMO) e fase II, 20 casos (após a instalação do programa ECMO com investimento em formação e equipamento). Foram considerados como desfechos primários: o desmame de ECMO e sobrevida até a alta hospitalar. Os resultados em ambas as fases foram comparados pelo teste Chiquadrado. Para identificar o impacto das diferentes variáveis,​ foi usada análise de regressão logística binária. Resultados: Na fase I, 9 pacientes (25%) foram desmamados da ECMO, mas apenas 2 (5,5%) tiveram alta. Na fase II, ECMO foi usado em 20 pacientes, o desmame foi possível em 17 deles (85%), com 9 (45%) altas hospitalares. Quando analisamos o impacto das diversas variáveis ​​sobre a sobrevida e desmame de ECMO, observa-se que a fase II foi um preditor independente de melhores resultados (P<0,001) e a necessidade de drenagem das cavidades esquerdas foi associada com pior sobrevida (P=0,045). Conclusão: O investimento na formação profissional e aperfeiçoamento de equipamentos melhorou significativamente os resultados de ECMO em nossa instituição.

Abbreviations, acronyms & symbols ABS ACT APTT CPB ECMO ELSO UFH

Aristotle Basic Score Activated clotting time Activated Partial Thromboplastin Time Cardiopulmonary bypass Extracorporeal membrane oxygenation Extracorporeal Life Support Organization Unfractionated heparin

Resumo Introdução: Falência ventricular pós-cardiotomia necessitando de suporte circulatório mecânico ocorre em cerca de 0,5% dos casos. Em nosso meio, o uso de ECMO tem aumentado nos últimos anos. Objetivo: Avaliar o impacto do investimento na formação profissional e melhoria dos equipamentos na taxa de desmame de ECMO e na sobrevida. Métodos: Estudo retrospectivo. Cinquenta e seis pacientes cardíacos pediátricos e/ou portadores de cardiopatias congênitas foram submetidos ao implante de ECMO pós-cardiotomia em nossa instituição entre novembro de 1999 e julho de 2014. Nós dividimos este período em duas fases: fase I, 36 casos (antes da

Descritores: Membrana de Oxigenação Extracorpórea. Avaliação de Resultado de Ações Preventivas. Cardiopatias Congênitas. Capacitação de Recursos Humanos em Saúde. Procedimentos Cirúrgicos Cardiovasculares.

INTRODUCTION

guidelines reinforce the importance of using appropriate equipment along with active and continued team training[8]. Patients that demand ECMO are definitely very sick and require a multidisciplinary approach. As it is a relatively new technology, specific staff training before they have contact with these kind of patients is mandatory. But sometimes these steps are skipped, specially in developing countries, due to lack of planning and budget regarding this concern. In our institution, ECMO has been used since 1999. As above mentioned, we have experienced all sort of drawbacks. However, in 2012, we started restructuring the institutional circulatory assistance program focusing on results improvement. Our initial investment was in team training according to ELSO guidelines and the purchase of specific equipment, especially for the pediatric population. This study aims to assess the impact of these measures on short-term results of patients undergoing post-cardiotomy ECMO in pediatric patients and patients with congenital heart disease.

The first use of extracorporeal membrane oxygenation (ECMO) as respiratory and cardiac support was in 1975[1]. Since then this therapy has significantly evolved its indications and results. However, the high cost of equipment, poor initial results and the need of training specialists have been avoiding ECMO to gain widespread usage in Brazil[2,3]. There are few alternatives for pediatric patients with failure to wean from cardiopulmonary bypass. The intra-aortic balloon pump and prolonged ventricular assist devices have very limited role in children because of sizing characteristics and pediatric patients’ physiology, such as high heart rate and elasticity of blood vessels in children[4]. That said, ECMO presents as the main alternative for the treatment of refractory post-cardiotomy cardiopulmonary failure[5]. International authors have been reporting satisfactory results with post-cardiotomy ECMO since the late 80’s[6]. In Brazil, ECMO has been applied consistently in a few centers, but the experience reported in the literature is still scarce[7]. According to data from equipment manufacturers, there were commercialized about 200 ECMO membranes in 2013. The Extracorporeal Life Support Organization (ELSO)

METHODS Retrospective study including all patients who had undergone post-cardiotomy ECMO [intraoperative or immediate

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postoperative period (within 24 hours) of pediatric heart surgery or surgery to correct congenital heart disease]. The study was approved by the institutional Ethics Committee (CEP-HC FMUSP 741.911). Between November 1999 and July 2014, 11,191 patients underwent cardiac surgery to correct congenital heart defects in our institution. In 56 (0.5%) of these patients ECMO was needed in the intraoperative period or within 24 hours after surgery.

performed a 40 hour ECMO specialist course. After that, these doctors have started training the intensive care nurses following the ECLS specialists’ guidelines. From that time on, Canadian specialists started repeating the 40 hour North-American ECMO specialist course inside our hospital once a year with the assistance of our specialists (nurses and doctors). Cannulation Full sternotomy was used and central cannulation performed in all cases. Cannulas were placed in the right atrium and ascending aorta. In cases where the drainage of left chambers was needed, it was chosen to open an interatrial communication or install a second drainage catheter into the left atrium. The sternum was kept away in all cases and the skin covered by silicon patch or directly approximated using a continuous running suture. The cannulas were exteriorized between skin approximation sutures.

Exclusion Criteria Patients in whom ECMO was indicated as rescue during cardiac arrest (E-CPR) or at a later period than 24 hours postoperatively were excluded from the analysis. Indication As occurs with most new technologies, its applicability has been modified over time, including improvement of results with accumulation of experience. The indication of ECMO occurred in patients that could not be weaned from the cardiopulmonary bypass (CPB) after clinical support optimization and when the dose of vasopressors and inotropes was progressively higher to maintain vital functions, with persistent metabolic acidosis within 24 hours.

Anticoagulation protocol Our protocol consists of an Unfractionated Heparin (UFH) loading dose of 50 to 100 units/kg followed by a 20 to 50 units/kg/hour maintenance dose. UFH dose is adjusted aiming an Activated Clotting Time (ACT) between 180 and 220 seconds, Activated Partial Thromboplastin Time (APTT) between 50 and 80 seconds and an anti-Xa between 0.3 and 0.6 units/mL. ACT is measured every two hours, APTT every 12 hours and anti-Xa daily. When it is not possible to wean the patient from cardiopulmonary bypass, half the dose of protamine is administered and ACT, APTT and anti-Xa levels above mentioned are pursued. If bleeding persists, no more protamine is administered, but other coagulation factors abnormalities are corrected.

Contraindication The presence of uncontrollable bleeding and other ECMO contraindications, hardly ever present in cardiac surgery patients, such as disabling neurological injury or intractable severe extra-cardiac disease. Division in two phases In 2012, there was the implementation of the circulatory assist team (Incor ECMO team), registered in ELSO under the number 276. These changes included investment in equipment and training. Therefore of that, we divided the patients into two groups: phase I (before the circulatory assist program) with 36 patients and phase II (after implementation of the program) with 20 patients. The oxygenator used during phase I was silicone membrane (Medtronic inc, Minneapolis, USA) and the pump was Bio-Pump® (Medtronic inc, Minneapolis, USA). Line pressures were not measured at that time and patients under 10 kg did not have a bridge in their circuits. During phase II the ECMO circuit was updated, the membrane was made of polymethylpentene (Maquet Getting Group, Rasttat, Germany) and the centrifugal pump changed to Rotaflow® (Maquet Getting Group, Rasttat, Germany) with less priming volume and less heat generation. Line pressure measurement was implemented, so was the bridge in circuits for patients under 10 kg. Staff training in 2012 consisted of two parts. First of all, a group of doctors went to Stollery Children’s Hospital and

Weaning protocol During phase I, weaning was based primarily on cardiac function recovery on echocardiography and clinical data (serum lactate, arterial pressure, central venous pressure, urine output). In phase II, measurement of left ventricle outflow tract VTI (Velocity Time Integral) in cm was added to the weaning protocol. This measurement is taken daily with full ECMO flow and 30% of ECMO flow. When it is more than 10 cm, weaning is planned, respecting all abovementioned parameters[9]. Hemodynamic stability should be assured for at least 6 hours with low flow. After this period, blood gas samples are collected and the echocardiographic examination is repeated. The patient is decannulated if it meets all the abovementioned criteria. After decannulation we rather not approximate the sternum at this time, in order to avoid compression of the heart cavities and to facilitate possible re-cannulation. Sternum closure is attempted after 24 hours of decannulation and clinical stability. It is important to re-connect the arterial and venous tubes immediately after

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decannulation and keep the membrane and the pump running for 24 hours, which avoid thrombus formation and allows re-connect the patient to the same circuit in case of clinical deterioration during these critical hours.

Parameters analyzed ECMO duration was compared between those who were weaned or died. Complications related to ECMO, survival to weaning and discharge home in both phases were analyzed. It was considered as weaning from ECMO when it was possible to perform decannulation and the patient didn’t die or returned to ECMO within 24 hours. Timing of cannulation was divided in perioperative cannulation and postoperative cannulation when it occurred within 24 hours after surgery.

Diagnosis and group comparison We listed the diseases treated surgically in Table 1. In order to assess if the groups were similar, we compared median age, weight, neonatal rate, gender, Aristotle Basic Score (ABS) and rate of palliative surgery in each group[10].

Statistical Analysis Normality test used was Shapiro-Wilk. Descriptive statistics data are presented as average plus or minus standard deviation for continuous variables with normal distribution and median with interquartile range (IQR) for non-normal distribution and ordinal variables. The comparison between groups including age, neonatal rate, gender, weight, time of cannulation, palliative surgery, left heart drainage and ABS was performed using non-parametric tests (Mann-Whitney and Chi-square). Binary Logistic regression was used to evaluate the impact of phase, age, neonatal rate, gender, weight, time of cannulation, palliative surgery rate, left heart drainage and ABS on weaning from ECMO and survival to hospital discharge results. It was considered significant a P value of <0.05. The statistical software used for analysis was SPSS v19.0 (IBM corporation, Armonk-New York; United States).

Table 1. List of diseases that led to surgery at each phase. Diagnosis Phase I Phase II (n= 36) (n=20) TGA 7 1 HLHS 7 1 ToF with PV agenesis 2 2 Truncus Arteriosus 3 1 AVSD 4 2 PA 3 2 Single Ventricle 3 1 Mitral valve disease 3 2 Dilated Cardiomiopathy 1 1 IAA 2 1 AVSD + ToF 0 1 ALCAPA 1 1 ccTGA 0 1 Restrictive Cardiomiopathy 0 1 ASD + VSD + PH 0 1 late post-op ToF PR 0 1

RESULTS

TGA=transposition of the great arteries; HLHS=hypoplastic left heart syndrome; ToF=tetralogy of Fallot; PV=pulmonary valve; AVSD=atrio-ventricular septal defect; IAA=interrupted aortic arch; ALCAPA=anomalous origin of the left coronary artery from the pulmonary artery; ccTGA=congenitally corrected transposition of the great arteries; ASD=atrial septal defect; VSD=ventricular septal defect; PH=pulmonary hypertension; Post-op=postoperative period; PR=pulmonary regurgitation

Comparison between groups didn’t show any statistically significant difference (Table 2). Nevertheless, median ABS in phase I was 10 (9.1-11) and in phase II was 9.3 (7.8-10). This result was borderline statistically different (P=0.05), so was the neonatal rate in both phases (38.9% x 15%; P=0.06). The surgeries performed in each group are listed in Table 3.

Table 2. Demographic and surgical characteristics of patients in phases I and II. Characteristics Age (days) (Median (IQR)) Weight (kg) (Median (IQR)) Neonates (n (%)) Male gender (n(%)) ABS (Median (IQR)) Palliatives (n (%)) Left drainage (n (%)) POI Timing (n(%))

Phase I (n=36) 90 (9.5-1637.5) 4.7 (3.2-17.1) 14 (38.9%) 22 (61.%) 10 (9.1-11) 10 (27.7%) 4 (11.1%) 11 (30.5%)

Phase II (n=20) 240 (67.5-2045) 5.6 (3.2-16.1) 3 (15%) 11 (55%) 9.3 (7.8-10) 7 (35%) 4 (20%) 2 (10%)

P value 0.17 0.57 0.06 0.66 0.05 0.57 0.36 0.08

IQR=interquartile range; ABS=Aristotle Basic Score; Palliative=palliative surgery; Left Drainage=need for drainage of the left cavities; POI Timing=ECMO implants that did not occur immediately post-bypass but within 24 hours of postoperative period

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The total time on ECMO in patients in whom weaning was possible didn’t differ between groups. Average time in phase I was 110.7±52.9 hours, while in the 17 weaned patients in stage II it was 182.2±117 hours (P=0.1). ECMO related complications were similar between groups (Table 4). In phase I, nine patients (25%) were weaned from ECMO, however, discharge from hospital occurred in only 2 (5.5%). Moreover, in the last 20 patients (phase II), it was possible to wean 17 patients from ECMO (85%, P<0.0001) and 45% (9 patients) was discharged from hospital (P=0.001) (Figure 1). Binary logistic regression revealed that the need for left cavities drainage didn’t impact ECMO weaning, but accounted for an increase in mortality (P=0.045, Table 5). Phase II was an independent predictor of ECMO weaning (P=0.001) and hospital discharge (P=0.01; Table 5).

Table 3. Details of surgical procedures performed in two phases. Surgery ASO Norwood procedure ToF + PV agenesis correction Truncus Arteriosus correction AVSD correction Rastelli procedure Damus-Kaye-Stensel procedure MV replacement Cardiac Transplant IAA correction AVSD + ToF correction ALCAPA correction + MV repair ASD + PV repair PV replacement Senning operation Extracardiac Fontan procedure Glenn procedure Rastelli + unifocalization

Phase I (n= 36) 7 7 2 3 4 3 1 3 1 2 0 1 0 0 0 1 1 0

Phase II (n=20) 0 1 2 1 2 1 1 3 2 1 1 1 1 1 1 0 0 1

DISCUSSION The use of ECMO as a bridge to post-cardiotomy recovery in children is an increasingly comprehensive reality. Large international centers report encouraging results[11], on the other hand, in our scenario, this has not always been replicated[7]. The high cost of technological development and the training of intensive care teams seem to be the greatest obstacles to this progress. Recently, the Toronto Sick Kids group reported their experience with ECMO emphasizing the importance of technological developments and team structure to improve performance[6]. The same group have had published some disappointing results almost ten years earlier[12] with a high incidence of neurological impairment and poor survival, which have led them to work on team performance and on improving technology. These investments were eventually paid off as they showed in their recent publication[6]. We clearly corroborate these findings in the present study, by demonstrating that investment in team training combined with a cost-effective investment in technology can bring significant benefits. In our service, despite our experience initiated in the late 90’s, very few members of the multidisciplinary team have demonstrated knowledge of materials and resources, particularly the direct patient caregivers. This scenario has completely changed with the continued training of these professionals and the subsequent improvement of the results. Recent studies using simulation in ECMO training have showed that this increases the confidence of professionals and increases the ability to solve problems[1,13].

ASO=arterial switch operation; ToF=tetralogy of Fallot; PV=pulmonary valve; AVSD=atrioventricular septal defect; MV=mitral valve; IAA=interrupted Aortic Arch; ALCAPA=anomalous left coronary artery from pulmonary artery; ASD=atrial septal defect

Table 4. Complications in post-cardiotomy ECMO in both phases. Complication Bleeding Neurological Renal

Phase I (n=36) 15 (41.7%) 3 (8.3%) 3 (8.3%)

Phase II (n=20) 4 (20%) 3 (15%) 2 (10%)

P value 0.1 0.4 0.8

Bleeding=need for re-thoracotomy and bleeding revision; Neurological =clinically and/or imaging detectable neurological injury; Renal=renal impairment with need for dialysis

Re-structuring of the Pediatric Circulatory Assist Program In early 2012, the institution made significant investment in infrastructure for circulatory assistance, mainly in team training, development of new protocols and purchase of technological devices.

Fig. 1 - Comparison Chart showing weaning from ECMO and survival results in phases I and II. P<0.0001 in the Chi-Square test comparing Phase I and II for OffECMO results; P=0.001 in the Chi-Square test comparing Phase I and II for survival to hospital discharge.

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Table 5. Binary Logistic regression analysis of variables in the results. Variables Phase II Age Weight Neonate Gender (M) Palliative Timing Left Drainage ABS

P value 0.001 0.22 0.28 0.19 0.77 0.21 0.78 0.88 0.86

Off-ECMO OR (95% CI) 26.8 (3.8-185.3) 1 (1-1.01) 0.9 (0.79-1.07) 3.9 (0.49-32.0) 0.78 (0.15-4.07) 4.06 (0.44-37.23) 0.79 (0.14-4.59) 0.84 (0.09-7.45) 0.96 (0.64-1.46)

P value 0.014 0.33 0.20 0.56 0.14 0.38 0.14 0.045 0.81

Survival OR (95% CI) 108.7 (2.5-4657.7) 0,99 (0.99-1,0) 1.2 (0.92-1.54) 2.9 (0.74-120.5) 0.19 (0.21-1.77) 0.31 (0.02 - 4.34) 22.9 (0.35-1523.7) 0.08 (0.007-0.94) 1.09 (0.54-2.24)

ABS=Aristotle Basic Score; Off-ECMO=patients weaned from ECMO that were alive and off-ECMO after 24 hours; OR=odds ratio; CI=confidence interval; Neonate=percentage of neonate patients in each sample; Gender (M)=percentage of male patients in each sample; Palliative=percentage of palliative surgeries in each sample; Timing=percentage of ECMO implants that did not occur immediatelly postbypass (perioperative) but within 24 hours of postoperative period; Left Drainage=need for drainage of the left cavities

Team Training In mid-2012, a group of four doctors from our institution took part on an ECMO training program in North America, more specifically in Edmonton, Canada, according to the ELSO training standards. From that time on, a task force was created to disseminate the knowledge acquired to everyone involved in ECMO assistance. In April 2013, six professionals from the US and Canada came to Brazil for the first time and replicated the North American ECMO specialist training course. Nine professionals from our institution were trained on this occasion, including five medical doctors, three nurses and one physiotherapist. Since then, continuing educational program was created to train all the nursing team focused on ECMO patient care. Several training and re-training programs were offered among their peers. A total of 24 institutional nurses were trained by ELSO guidelines and became able to assist patients on ECMO. Cognitive and practical tests were applied after each training session. In addition, we have performed simulated scenarios focused on training all multidisciplinary team in order to emphasize the importance of teamwork, so necessary in the care of these patients.

safe weaning. There was also significant progress of oxygenators, which now have a smaller priming, tolerate higher pressures, have greater durability and ability to filter possible air embolism or clots. The most modern centrifugal pumps will operate a smaller priming, provide less heat and therefore less damage to the blood elements. “Sprinter-cartâ€?: The purchase of two minimized supporting devices called sprinter carts, which accommodates all ECMO equipment with specific location for every device needed for ECMO (centrifugal pump console, centrifugal pump head, hand crank, heat exchanger, membrane oxygenator, pressure monitors, flow meters and heparin infusion pump) allowing ECMO to occupy the smallest possible space on the bedside and facilitate patient transport to exams and interventions. Pressure Monitors: specific pressure monitors of the ECMO circuit (negative venous pressure, pre-membrane pressure and post-membrane pressure) that were not monitored before, were incorporated in the second phase. Post-bridge arterial flowmeter: flowmeter suitable for pediatric tubing (Âź inch), which monitors the flow in the arterial line after the bridge. Measuring the flow that actually goes to the patient, and was incorporated into pediatric circuit in phase II. Our results in Phase I were not satisfactory: we attributed this to staff long learning curve, use of non-ideal equipment and no optimization of human resources. Fairly common obstacles in our environment[3,4,7]. However, with planning and structuring of ECMO care, represented herein by phase II, it was possible to obtain results similar to those reported in the literature[6,11]. We aim to further enhance these results, especially regarding hospital discharge. Some authors have reported survival over than

Specific equipment Disposable: The disposable material including centrifugal pump, an oxygenation membrane and line circuit with the extensions has evolved considerably over the years. Considering the pediatric circuit, there was the addition of the communication bridge between the arterial and venous lines, which provides a better malleable flow, minimizing the risk of thrombosis in the circuit and allows a more gradual and

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60% in this population[11], however, a survival rate of 50% is accepted as satisfactory in the literature[6,8]. Although we have not identified a higher incidence of thoracotomy for bleeding in the first phase, we realized when evaluating the medical records, that bleeding represented a significant problem in phase I, since it was responsible for many early ECMO discontinuations. Currently, better membranes and pumps, leading to less consumption of coagulation factors and more accurate care, account for better hemostasis management and overall results[14,15]. However, bleeding persists as the most common complication in most services as in ELSO recordings[6,8]. We didn’t notice any significant difference in time of circulatory support between phases in patients weaned from ECMO. There was a tendency of shorter runs in phase II and it was probably caused by a more structured weaning protocol. Three patients could not be weaned from ECMO in Phase II, one of which was assisted for 28 days and the device was turned off for non-recovery of ventricular function and occurrence of multiple organ failure, preventing the transplant. In the other two cases, both low weight, one was an eight monthold, 3 Kg cardiomyopathy baby with high immune panel, who underwent heart transplantation and had hyperacute humoral rejection. This patient handling was less than 48 hours since the left ventricle contractility was extremely poor, and even with anticoagulation and draining the left atrium, it was observed recurrent intraventricular thrombus formation, so ECMO was turned off. The other was a neonate who underwent correction of interrupted aortic arch and had a small aortic annulus and presented low cardiac output syndrome. This baby suffered massive cerebral hemorrhage after 4 days assisted and ECMO was discontinued due to reserved prognosis. It is known that neurological injuries are a relatively common complication in these patients and was directly responsible for death in four of our patients[12]. Two of the survivors in this series had significant neurological deficits, however, a satisfactory quality of life is observed in both of them, as for the other survivors. Recent studies have shown that quality of life of ECMO survivors is similar to other congenital heart patients[16]. Among the 17 patients weaned in phase II, 15 have recovered ventricular function while two showed no ventricular recovery after 72 hours of ECMO and were listed and transplanted. Both showed good evolution and could be discharged home. The most frequent complication in both phases was bleeding requiring a thoracotomy for hemostasis revision in 15 patients (41.7%) in phase I and 4 patients in phase II (20%) (P=0.14). The occurrence of detectable neurological complications occurred in three patients in Phase I (8.3%). In two of them ECMO was discontinued, the other was decannulated, but came to death four days later. In phase II, three patients had neurological lesions (15%; P=0.6). In one of them ECMO was turned off by major cerebral hemorrhage with brain death. The other two were discharged home with

hemiparesis. Both are being followed with partial remission of the deficit. Regarding anticoagulation protocol, the main difference between phase I and II was the daily measurement of anti-Xa, that has a better correlation to heparin levels than ACT and APTT[17]. Renal impairment and need for dialysis during phase I occurred in three patients (8.3%), while stage II dialysis was used in two phase II patients (10%; P=0.9). The drainage of the left chambers was performed in 4 patients in stage I (11%), in three it was performed surgically opening an atrial septal defect and a ventricular septal communication associated with atrial septal defect in the other, since this was a pulmonary atresia with hypoplastic pulmonary arteries and right ventricular dysfunction. In phase II, left drainage was achieved with the placement of additional drainage cannula into the left atrium in three patients (15%; P=0.7) in which the drainage of the left cavities was mandatory because of very important left ventricular dysfunction. In only one phase II patient, the creation of an atrial septal communication was performed. This was a patient with preoperative diagnosis of large atrial septal defect and pulmonary artery aneurysm who underwent corrective surgery and evolved with refractory pulmonary hypertension crisis. Echocardiography performed on the first postoperative day revealed an apical ventricular septal defect with right-left shunt that was not detected preoperatively. This patient returned to surgery in poor clinical conditions, arterial saturation of 65% and with two resuscitated cardiac arrests. In surgery it was decided to re-open the ASD and install ECMO. Weaning was possible after 5 days with arterial oxygen saturation around 80%, however, the patient died due to infection 16 days after decannulation. The need for left cavities drainage was a predictor of mortality in our patients. This is not surprising because these patients tend to present with worse left ventricular function pre-ECMO. Repositioning of the cannulas was necessary in two patients. A phase I patient needed right atrial cannula repositioning to improve drainage and one phase II patient was submitted to repositioning of the aortic cannula. Study Limitations This is a retrospective study with all its limitations. We tried to make sure if the groups were comparable and noticed that Phase I cases had a tendency to be more complex (more neonates and higher ABS; P=0.06 and P=0.05). On the other hand, logistic regression didn’t show impact of these variables in the results, corroborating previous studies[18]. CONCLUSION The structuring of an ECMO service with suitable equipment for the pediatric population and team training was able to increase the probability of post-cardiotomy ECMO weaning and survival.

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8. Extracorporeal Life Support Organization. Guidelines [cited 2015 Jun 8]. Available from: http://www.elso.org/resources/ guidelines.aspx

Authors’ roles & responsibilities LAM LFC CT JGP VAG NM FRBGG MBJ

Analysis and/or interpretation of data; final approval of the manuscript; implementation of projects and/or experiments Analysis and/or interpretation of data; final approval of the manuscript; study design; implementation of projects and/or experiments Conception and design; implementation of projects and/or experiments Final approval of the manuscript; implementation of projects and/or experiments Conduct of operations and/or experiments; manuscript writing or critical review of its content Analysis and/or interpretation of data; study design Conception and design; implementation of projects and/or experiments Analysis and/or interpretation of data; final approval of the manuscript; study design; implementation of projects and/or experiments

9. Aissaoui N, Luyt CE, Leprince P, Trouillet JL, Léger P, Pavie A, et al. Predictors of successful extracorporeal membrane oxygenation (ECMO) weaning after assistance for refractory cardiogenic shock. Intensive Care Med. 2011;37(11):1738-45. 10. Lacour-Gayet F, Clarle D, Jacobs J, Gaynor W, Hamilton L, Jacobs M, et al.; Aristotle Committee. The Aristotle score for congenital heart surgery. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2004;7:185-91. 11. Beiras-Fernandez A, Deutsch MA, Kainzinger S, Kaczmarek I, Sodian R, Ueberfuhr P, et al. Extracorporeal membrane oxygenation in 108 patients with low cardiac output - a singlecenter experience. Int J Artif Organs. 2011;34(4):365-73.

REFERENCES

12. Chow G, Koirala B, Armstrong D, McCrindle B, Bohn D, Edgell D, et al. Predictors of mortality and neurological morbidity in children undergoing extracorporeal life support for cardiac disease. Eur J Cardiothorac Surg. 2004;26(1):38-43.

1. Chan SY, Figueroa M, Spentzas T, Powell A, Holloway R, Shah S. Prospective assessment of novice learners in a simulationbased extracorporeal membrane oxygenation (ECMO) education program. Pediatr Cardiol. 2013;34(3):543-52.

13. Burkhart HM, Riley JB, Lynch JJ, Suri RM, Greason KL, Joyce LD, et al. Simulation-based postcardiotomy extracorporeal membrane oxygenation crisis training for thoracic surgery residents. Ann Thorac Surg. 2013;95(3):901-6.

2. Bartlett RH, Gazzaniga AB, Jefferies MR, Huxtable RF, Haiduc NJ, Fong SW. Extracorporeal membrane oxygenation (ECMO) cardiopulmonary support in infancy. Trans Am Soc Artif Intern Organs. 1976; 22:80-93.

14. McMullan DM, Emmert JA, Permut LC, Mazor RL, Jeffries HE, Parrish AR, et al. Minimizing bleeding associated with mechanical circulatory support following pediatric heart surgery. Eur J Cardiothorac Surg. 2011;39(3):392-7.

3. Dearani JA, Neirotti R, Kohnke EJ, Sinha KK, Cabalka AK, Barnes RD, et al. Improving pediatric cardiac surgical care in developing countries: matching resources to needs. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2010;13(1):35-43.

15. Hoashi T, Kagisaki K, Yamashita K, Tatsumi E, Nishigaki T, Yoshida K, et al. Early clinical outcomes of new pediatric extracorporeal life support system (Endumo (2000) in neonates and infants. J Artif Org. 2013;16(3):267-72.

4. Neirotti R. Paediatric cardiac surgery in less privileged parts of the world. Cardiol Young. 2004;14(3):341-6. 5. Paul Collison S, Singh Dagar K. The role of the Intra-aortic balloon pump in supporting children with acute cardiac failure. Postgrad Med J. 2007;83(979):308-11.

16. Costello JM, O’Brien M, Wypij D, Shubert J, Salvin JW, Newburger JW, et al. Quality of life of pediatric cardiac patients who previously required extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2012;13(4):428-34.

6. Kotani Y, Honjo O, Davey L, Chetan D, Guerguerian AM, Gruenwald C. Evolution of technology, establishment of program, and clinical outcomes in pediatric extracorporeal membrane oxygenation: the “sickkids” experience. Artif Organs. 2013;37(1):21-8.

17. Nankervis CA, Preston TJ, Dysart KC, Wilkinson WD, Chicoine LG, Welty SE, et al. Assessing heparin dosing in neonates on venoarterial extracorporeal membrane oxygenation. ASAIO J. 2007;53(1):111-4.

7. Atik FA, Castro RS, Succi FM, Barros MR, Afiune C, Succi G de M, et al. Use of centrifugal pump and extracorporeal membrane oxygenation as cardiopulmonary support in pediatric cardiovascular surgery. Arq Bras Cardiol. 2008;90(4):216-20.

18. Polimenakos AC, Wojtyla P, Smith PJ, Rizzo V, Nater M, El Zein CF, et al. Post-cardiotomy extracorporeal cardiopulmonary resuscitation in neonates with complex single ventricle: analysis of outcomes. Eur J Cardiothorac Surg. 2011;40(6):1396-405.

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Dias AEMSAS, et al. - Oxidative stress in coronary artery bypass surgery ORIGINAL ARTICLE

Oxidative stress in coronary artery bypass surgery Estresse oxidativo na cirurgia de revascularização miocárdica

Amaury Edgardo Mont’Serrat Ávila Souza Dias1, MD, MSc; Petr Melnikov2, PhD; Lourdes Zélia Zanoni Cônsolo1, MD, PhD

DOI: 10.5935/1678-9741.20150052

RBCCV 44205-1659

Abstract Objective: The aim of this prospective study was to assess the dynamics of oxidative stress during coronary artery bypass surgery with cardiopulmonary bypass. Methods: Sixteen patients undergoing coronary artery bypass grafting were enrolled. Blood samples were collected from the systemic circulation during anesthesia induction (radial artery - A1), the systemic venous return (B1 and B2) four minutes after removal of the aortic cross-clamping, of the coronary sinus (CS1 and CS2) four minutes after removal of the aortic cross-clamping and the systemic circulation four minutes after completion of cardiopulmonary bypass (radial artery - A2). The marker of oxidative stress, malondialdehyde, was measured using spectrophotometry. Results: The mean values of malondialdehyde were (ng/dl): A1 (265.1), B1 (490.0), CS1 (527.0), B2 (599.6), CS2 (685.0) and A2 (527.2). Comparisons between A1/B1, A1/CS1, A1/B2, A1/ CS2, A1/A2 were significant, with ascending values (P<0.05). Comparisons between the measurements of the coronary sinus and venous reservoir after the two moments of reperfusion (B1/ B2 and CS1/CS2) were higher when CS2 (P<0.05). Despite higher values ​​after the end of cardiopulmonary bypass (A2), when compared to samples of anesthesia (A1), those show a down-

ward trend when compared to the samples of the second moment of reperfusion (CS2) (P<0.05). Conclusion: The measurement of malondialdehyde shows that coronary artery bypass grafting with cardiopulmonary bypass is accompanied by increase of free radicals and this trend gradually decreases after its completion. Aortic clamping exacerbates oxidative stress but has sharper decline after reperfusion when compared to systemic metabolism. The behavior of thiobarbituric acid species indicates that oxidative stress is an inevitable pathophysiological component.

Federal University of Mato Grosso do Sul Hélio Mandeta Medical School, Campo Grande, MS, Brazil. 2 Moscow State Universit, Moscow, Russia.

Correspondence address: Amaury Edgardo Mont’Serrat Ávila Souza Dias Rua Fortuna 142, Caranda Bosque - Campo Grande, MS, Brazil Zip code: 79002-942 E-mail: amaurymont@hotmail.com

Descriptors: Cardiopulmonary Bypass. Oxidative Stress. Myocardial Revascularization. Resumo Objetivo: O objetivo deste estudo prospectivo foi avaliar a dinâmica do estresse oxidativo durante a cirurgia de revascularização miocárdica com circulação extracorpórea. Métodos: Participaram 16 pacientes submetidos à revascularização miocárdica. As amostras de sangue foram coletadas da circulação sistêmica, no momento da indução anestésica (artéria radial - A1), do retorno venoso sistêmico (B1 e B2), quatro

1

This study was carried out at Universidade Federal do Mato Grosso do Sul, Hélio Mandeta Medical School, Campo Grande, MS, Brazil.

Article received on August 11th, 2014 Article accepted on March 9th, 2015

No financial support.

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reservatório venoso após os dois momentos de reperfusão (B1/ SC1 e B2/SC2) foram mais elevadas no momento SC2 (P<0,05). Apesar dos valores mais elevados após o término da circulação extracorpórea (A2), quando comparadas às amostras da indução anestésica (A1), aqueles apresentam tendência de queda quando comparadas as amostras do segundo momento de reperfusão (SC2) (P<0,05). Conclusão: As dosagens de malondialdeído mostram que a revascularização miocárdica com circulação extracorpórea é acompanhada de aumento de radicais livres com tendência deste diminuir progressivamente após seu término. O pinçamento aórtico exacerba o estresse oxidativo, porém apresenta queda mais acentuada após a reperfusão quando comparadas ao do metabolismo sistêmico. O comportamento das espécies reativas ao ácido tiobarbitúrico indica que o estresse oxidativo é um componente patofisiológico inevitável.

Abbreviations, acronyms & symbols CPB Cardiopulmonary bypass FR Free radicals MDA Malondialdehyde TBARS Reactive species thiobarbituric acid

minutos após a remoção do pinçamento aórtico, do seio coronariano (SC1 e SC2), quatro minutos após a remoção do pinçamento aórtico, e da circulação sistêmica, quatro minutos após finalização da circulação extracorpórea (artéria radial - A2). O marcador do estresse oxidativo, malondialdeído, foi dosado utilizando espectrofotometria. Resultados: Os valores médios de malondialdeído foram (ng/ dl): A1 (265,1), B1 (490,0), SC1 (527,0), B2 (599,6), SC2 (685,0) e A2 (527,2). As comparações entre A1/B1, A1/SC1, A1/B2, A1/SC2, A1/A2 foram significativas, com valores ascendentes (P<0,05). As comparações entre as dosagens do seio coronário e

Descritores: Revascularização Miocárdica. Estresse Oxidativo. Circulação Extracorpórea.

INTRODUCTION

The formation of free radicals can compromise several cell elements, causing protein denaturation, DNA chain breaks, enzymatic inactivation and lipid peroxidation[12]. The damage to lipids induces lipid peroxidation. One of the most popular products of lipid peroxidation is malondialdehyde (MDA)[13], which is the final product of non-enzymatic degradation of polyunsaturated fatty acids. High MDA levels increase the formation of lipoperoxide and indicate increased lipid peroxidation[14]. The membranes are mainly composed of phospholipids and proteins. Changes in membrane lipids are among the main events during ischemia and reperfusion, thus losing the selectivity in ion exchange, release of hydrolytic enzymes, formation of cytotoxic products, ending with cell death[15,16]. There are some methods of measurement of free radicals, among which stands out the detection of reactive species thiobarbituric acid (TBARS), which aims to detect lipid peroxidation of the cell membrane[17]. We know that in cardiac surgery, the use of cardiopulmonary bypass causes global systemic ischemia, leading to exacerbate the release of free radicals. In addition, some intraoperative techniques adopt ischemia and reperfusion as myocardial protection method, either associated with various types of cardioplegic solutions or just under mild hypothermia. Thus, the careful study of ischemia-reperfusion process is of paramount importance, since the techniques adopted during CABG are peculiar in the induction of this process,

For several decades, the myocardial ischemic syndromes are the subject of various investigations into the etiology, pathogenesis, progression and treatment in order to achieve the best outcome. Despite the numerous clinical trials in order to shorten the ischemia and therefore limit the extent of injury, the reintroduction of oxygen to an ischemic means initiates a complex chain of events leading to additional tissue injury[1,2], which do not ensure the maintenance of ventricular function. During normal myocyte metabolism, complete reduction of an oxygen molecule in the electron transport chain, requires addition of four electrons. Due to its electronic conformation, oxygen tends to receive an electron at a time (monovalent reduction), culminating in the formation of reactive intermediates of oxygen - reactive oxygen species metabolism (ROMs), such as superoxide radicals (O2-·) hydroperoxyl (HO2·) and hydroxyl (OH·) and hydrogen peroxide (H2O2)[3]. The reactive oxygen species are important contributors to the reperfusion injury[4,5]. After the onset of reperfusion there is a respiratory “explosion” by the input of O2 lasting for several minutes and persistently elevated superoxide production[6,7]. Studies have demonstrated that the generation of free radicals (FR) is maximum in 3 to 5 minutes of reperfusion and lasting up to 3h[8,9], which significantly contributes to the myocardial depression[10,11].

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and that intermittent aortic clamping can also contribute to this mechanism.

Preto - SP) were used and priming calculated as the perfusion hematocrit – 20 mg/dl. The electrolyte and metabolic balance was maintained in accordance with the metabolic needs of the patient during standard procedure. The perfusion technique adopted was alpha pH stat. Anesthesia was performed according to established protocols, but the use of possible free radical suppressor as ascorbic acid and n-acetylcysteine were not used.

General Objectives Assessing the dynamics of concentrations of thiobarbituric acid reactive substances during coronary artery bypass grafting with cardiopulmonary bypass and intermittent aortic clamping. Specific objectives Determining the concentrations of thiobarbituric acid reactive substances from the systemic venous return during cardiopulmonary bypass, and venous return from the coronary sinus after myocardial reperfusion. Assessing the dynamics of dosages of thiobarbituric acid reactive substances during the procedure. Comparing the dynamic element studied between assays from the systemic circulation and the coronary sinus.

Blood and laboratory analysis Moments of collection were: A1 - blood collected at time of anesthetic induction sample of the radial artery. A2 - blood collected four minutes after completion of CPB - sample of the radial artery. B1 - blood collected from the venous line of the cava after 4 minutes of the first unclamping. B2 - blood collected from the venous line of the cava after 4 minutes of the second unclamping. CS1 - blood from the venous return of the coronary sinus after 4 minutes of the first unclamping. CS2 - blood collected from the coronary sinus venous return after 4 minutes of the second unclamping. Blood samples were collected in polypropylene syringes and immediately transferred to vacuum tubes (BD Vacutainer Systems, Becton, Dickinson & Co). Serum was separated by centrifugation (3.000×g, 15 min), and transferred to demineralized Eppendorf tubes, and stored at -18°C for later determination of malondialdehyde. All materials, plastics or glasses were immersed for 24 hours in 5% Extran solution (Merck), rinsed and immersed for at least 24 hours in a 10% ultrapure solution of nitric acid (Merck) for waste decontamination. Then, they were washed with ultrapure water (Milli-Q, Millipore, Bedford, USA) and dried at 40°C. The plasmatic concentrations of the substances that react with thiobarbituric acid (TBARS) were measured by spectrophotometric method. The test used to evaluate cellular damage by lipid peroxidation is based on the study by Percário et al.[17]. The volume of 1 ml TBA (thiobarbituric acid) (10 nM/l) was added to 0.5 ml of the sample. A standard solution consisting of 1 ml TBA (10 nM/l) and 0.5 ml of MDA was prepared (20 nM/L). A third solution containing 1 ml of TBA (10 nM/l) and 0.5 ml of water, served as background reading of the spectrophotometer. These solutions were heated in water bath at 94°C for 1 hour and then cooled in running water for 5 minutes. To block reaction we added 4 ml of n-butyric alcohol in each tube. The tubes were vortexed for complete extraction of the MDA into the organic phase of the system, then centrifuged at 2500 rpm for 10 minutes. At this time, there is phase separation, and 3 ml of the organic phase (surface) was aspirated for spectrophotometer reading.

METHODS The study was approved by the Medical Ethics Committee of the Universidade Federal do Mato Grosso do Sul (Protocol 1926) and the written informed consent form was signed by each patient participating in the study. It was a prospective study performed at the Cardiovascular Surgery Service of the University Hospital of the Universidade Federal do Mato Grosso do Sul. Population The study included sixteen patients, 5 females and 11 males, who underwent coronary artery bypass grafting with cardiopulmonary bypass for making 2 or more grafts. Patients with acute or chronic renal failure, diabetes mellitus, heart rate in atrial fibrillation, patients with dilated cardiomyopathy or associated valvular lesions, patients undergoing emergency surgery or patients using any medication suppressing free radicals as vitamin C, n-acetylcysteine, allopurinol, immunomodulatory or corticosteroids not were included. Cardiopulmonary bypass After pattern longitudinal median sternotomy, for cardiopulmonary bypass (CPB) a cannula in the ascending aorta was installed and double venous and coronary sinus drainage were performed in order to collect selective samples. The CPB was performed in mild hypothermia (32°C) and hemodilution. The technique for revascularization was intermittent aortic cross-clamping, adopted as routine by the Cardiovascular Surgery Service of the University Hospital of the Universidade Federal do Mato Grosso do Sul. Roller pump in the arterial line and hollow fiber membranes oxygenators with arterial line filter (Braile Biomédica - São José do Rio

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The reading was performed at 532 nm. The final amount of MDA in ng/dl is obtained by using the following formula:

Table 3 shows the comparisons between assays of TBARS during anesthetic induction and the venous line and coronary sinus with 4 min of reperfusion after the 2nd aortic unclamping, or that is, A1/B2 and A1/CS2. The analysis was performed in each patient, using the Student t test for paired data.

MDA = A average x F, where A average = (A1+A2)/2. F=4406.1/A Standard MDA, where A is absorbance.

Table 3. Comparison of the dosages of TBARS (ng/ml) between the times A1 - B2 and A1 - CS2*.

Statistical analysis Comparisons of measurements of TBARS in the times of aortic clamping in the radial artery, venous return and coronary sinus were performed with the Student t test for paired data at the 95% level of significance. The tests involving correlation between variables were performed via linear correlation coefficient of Pearson and its respective t-Student test. The normality of the data, via criteria of Kolmogorov-Smirnov also at the 95% level of significance was tested.

TBARS

TBARS

Mean ± SD 38.0 - 70.0 (51.6±9.7) 7.0 - 13.0 (9.9±2) 7.0 - 15.0 (9.9±2.5) 40.0 - 120.0 (68.1±23.2)

<0.001

Time B1 B2 CS1 CS2

Mean ± SD 490±360.9 599.6±346.7 527±358.7 684.9±386.7

P 0.008 <0.001

*B1=systemic venous return, four minutes after the first unclamping; CS1=coronary sinus, four minutes after the first unclamping; B2=systemic venous return, four minutes after the second unclamping; CS2=coronary sinus, four minutes after the second unclamping; TBARS=reactive species thiobarbituric acid

CPB=cardiopulmonary bypass

The data in Table 2 show the analysis comparing each individual from the anesthetic induction and after the first aortic unclamping (4 min reperfusion), or induction of anesthesia/venous line (A1/B1) and induction of anesthesia/ Coronary sinus (A1/CS1). In the table are shown the average values for each site, the average difference found and evaluation of significance by Student’s t test for paired data.

Table 5 presents the comparisons of TBARS levels between the last period of reperfusion and after the end of cardiopulmonary bypass, or that is, B2/A2 and CS2/A2. The analysis was performed in each patient, using the Student t test for paired data. Table 5. Comparison of the dosages of TBARS (ng/ml) between the moments B2 - A2 and CS2 - A2*.

Table 2. Comparison of the dosages of TBARS (ng/ml) between the times A1 - B1 and A1 - CS1*.

TBARS

<0.001

Table 4. Comparison of the dosages of TBARS (ng/ml) between the moments B1 - B2 and CS1 - CS2*.

Table 1. Ejection fraction (%), aortic clamping time and CPB time.

Mean ± SD 265.1±233.5 490±360.9 265.1±233.5 527±358.7

P

Comparisons of TBARS levels between the two periods of reperfusion, or that is, between samples collected in the venous line and coronary sinus after 4 min the removal of each of the two aortic clamping performed (B1/B2 and CS1/ CS2) are presented in Table 4. The analysis was performed in each patient, using the Student t test for paired data.

This study evaluated 16 patients being 5 females (31.2%) and 11 males (68.8%) with mean age of 60±8.6 years (mean±SD). The ventricular ejection fraction prior to surgery was 51.6±9.7. The total time of cardiopulmonary bypass was 68.1±23.2 min. The average times of the 1st and 2nd aortic clamping were 9.9±2.0 min and 9.9±2.5 min, respectively (Table 1).

Time A1 B1 A1 CS1

Mean ± SD 265.1±233.5 599.6±346.7 265.1±233.5 684.9±386.7

*A1=anesthetic induction; B2=systemic venous return, four minutes after the second unclamping; CS2=coronary sinus, four minutes after the second unclamping; TBARS=reactive species thiobarbituric acid

RESULTS

Parameters Ejection fraction 1st Clamping time (min) 2nd Clamping time (min) CPB time (min)

Time A1 B2 A1 CS2

P TBARS

<0.001 <0.001

Time B2 A2 CS2 A2

Mean ± SD 599.6±346.7 494.5±336.7 684.9±386.7 494.5±336.7

P 0.104 0.007

*B2=systemic venous return, four minutes after the second unclamping; CS2=coronary sinus, four minutes after the second unclamping; A2=4 minutes after completion of CPB; TBARS=reactive species thiobarbituric acid

*A1=anesthetic induction; B1=systemic venous return, four minutes after the first unclamping; CS1=coronary sinus, four minutes after the first unclamping; TBARS=reactive species thiobarbituric acid

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Table 6 presents the comparisons of TBARS levels between the venous line and the coronary sinus, after the two moments of reperfusion collected after 4 minutes of each unclamping, or that is, B1/CS1, B2/CS2. The analysis was performed in each patient, using the Student t test for paired data.

tional levels. The age group also does not contradict the data already known from the literature. The CPB used during cardiac surgery triggers an inflammatory reaction and consequent oxidative stress that is directly related to its duration[18]. In the present study, the mean CPB time was 68 minutes consistent with other studies[18-20]. Three patients required CPB time greater than 90 min due to the need for more grafts. However there was no correlation with perioperative complications. It is known that the inflammatory response related to the CPB is time dependent and that is closely related to oxidative stress, which could result in high oxidative stress measurements. Despite this assumption, this study and others published in the literature[18-20], since they have lower CPB time of 120 min, there was no evidence positive relationship between CPB time and oxidative stress. The metabolic parameters measured during the entire surgical procedure remained within limits compatible with the intraoperative stability. The reintroduction of blood in the coronary circulation after ischemia period produced by CPB and aortic clamping can lead to oxidative stress formation induced by oxygen free radicals and other ROMs, which can result in cellular injury. Ragab et al.[21] evaluated a total of 65 patients with unstable angina and acute myocardial infarction, determined the MDA levels in the acute phase of the syndrome and found high values with respect to the control group. Patients in the present study had normal levels of MDA (265.1 ng/ml) at time A1 (Figure 1), indicating that the previous acute ischemic event has been alleviated. Thus, the stabilization period adopted in the clinical treatment of the patient is essential for mitigation of the oxidative stress produced. It has been shown that patients undergoing CABG have no increase in TBARS between anesthetic induction and initiation of CPB. This proves by itself, that the surgical trauma is not responsible for the increased oxidative stress[19,22,23]. This observation enabled this study, neglecting the analytical dosage between the two mentioned moments. In this study, the overall results were similar to the literature data known beforehand. A comparison of assays performed in the moments A1/B1 and A1/CS1 (Figure 1) allows discovering a significant increase in TBARS levels. This can be considered as an indication that cardiopulmonary bypass is, in fact, an activation inductor of oxidative stress. Recent literature includes data regarding the relationship between oxidative stress, lipid peroxidation and ultrastructural myocardial damage in patients with chronic coronary artery disease undergoing coronary artery bypass surgery. Thus, after the restoration of coronary perfusion, Milei et al.[24] performed the determinations of oxidative stress and ultrastructural injury. The authors evaluated the TBARS production in the 5th and 20th min. after aortic unclamping, both from the coronary sinus effluent as the systemic circulation. It was observed that, in the

Table 6. Comparison of dosages of TBARS (ng/ml) between the moments B1 - CS1 and B2 - CS2*. Unclamping TBARS

1st 2nd

Time B1 CS1 B2 CS2

Mean ± SD 490±360.9 527±358.7 599.6±346.7 684.9±386.7

P 0.10 0.03

*B1=systemic venous return, four minutes after the first unclamping; CS1=coronary sinus, four minutes after the first unclamping; B2=systemic venous return, four minutes after the second unclamping; CS2=coronary sinus, four minutes after the second unclamping; A2=4 minutes after completion of cardiopulmonary bypass; TBARS=reactive species thiobarbituric acid

Table 7 compares the dosages of TBARS between anesthetic induction and after the end of cardiopulmonary bypass, or that is, A1/A2. The analysis was performed in each patient, using the Student t test for paired data. Table 7. Comparison of dosages of TBARS (ng/ml) between the moments A1- A2*. Element TBARS

Time A1 A2

Mean ± SD 265.1±233.5 494.5±336.7

P <0.001

*A1=anesthetic induction; A2=4 minutes after completion of cardiopulmonary bypass; TBARS=reactive species thiobarbituric acid

DISCUSSION During cardiac surgery with cardiopulmonary bypass, a series of inflammatory and immunological changes occur triggering oxidative stress. In non-physiological conditions during CPB, due to changes related to ischemia and reperfusion, there is an increase in free radicals and ROMs. In myocardial ischemic syndromes, it is well established that oxygen reintroduced in the myocardium during reperfusion causes significant injury. This stress is one of the initiators of this resulting myocardial damage[1,2]. Patients who met the criteria for this study were suffering from acute coronary syndrome with classic indications of myocardial revascularization. The time interval between onset of symptoms of acute coronary syndrome, or that is, from the diagnosis until the surgical treatment was 7 to 10 days. This period corresponds to the time required to optimize the treatment and stabilization of the clinical condition of patients. Our study has shown the prevalence of male patients similar to statistical indices established both at global and na-

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coronary sinus and the systemic circulation, the TBARS concentrations were similar in both moments, concluding that the isolated myocardial production of oxidizing substances was not greater than the systemic circulation. It is noteworthy that the first of those moments roughly corresponds to the B1 moment of our study, even if they have different aortic clamping times. Although the technique adopted was not exactly the same, the results of determination of TBARS are in agreement with the data from other methodologies. As follows from the results of this study, in the comparison between B1 and CS1, there are no significant differences in plasma TBARS levels of both the venous blood line as the coronary sinus collected after the first unclamping. This clearly demonstrates that cross-clamping does not increase the systemic oxidative stress in addition to the already installed. Akila et al.[18] performed a study comparing coronary artery bypass grafting with and without cardiopulmonary bypass in patients not infarcted and with preserved ventricular function. The average time of myocardial ischemia in the “on pump” group was 44.4 min and the CPB time was 65.6 min. It was concluded that in patients undergoing cardiopulmonary bypass, oxidative stress is higher in this group after 15 and 60 min, returning to levels similar to “off pump” patients 24 hours after aortic unclamping. Despite not having been the objective of Akila et al.[18], by thoroughly analyzing their results, we can extrapolate the data in the published tables. This allows noting that in the “on pump” subgroup, the 5th

min of reperfusion does not present significant increase in TBARS levels, however the increase was progressive. This becomes more evident in the 15th and 60th min, always presenting ascending pattern. This deviates from our study, since it is observed a significant increase in TBARS levels after 4 min of aortic unclamping, both in the systemic circulation (venous line), and the coronary sinus (coronary circulation). In addition, oxidative stress is accentuated in the second moment of reperfusion and presents downward trend after 4 min of the completion of cardiopulmonary bypass (A2) (Figure 1). These differences may be due to the fact that, in the study by Akila et al.[18], the average time of myocardial ischemia was approximately 45 min, while in this study it was approximately 20 min. Thus, a longer ischemic time would entail a tendency to perpetuate the oxidative stress and therefore progressively higher levels of TBARS. However, this would tend to return to baseline levels after 24 hours of aortic unclamping[18]. In this study the extent of TBARS after 24 hours was not measured, since the aim was to compare coronary reperfusion with systemic reperfusion, where maintaining another catheter in the coronary sinus allocated would bring risk due to the greater invasiveness of the patient. However, there was a downward trend in TBARS concentrations at the time A2, which probably remained as the triggering factors of oxidative stress had been removed. It is possible that brief episodes of

Fig. 1 - Schematic representation of the dynamics of TBARS concentrations. (↑ ↓) means the variation signal.

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ischemia-reperfusion imposed by intermittent aortic clamping have promoted a myocardial preconditioning, thereby allowing a higher tolerance to oxidative stress, and shortening the time of TBARS levels reduction[25]. Matata et al.[19] compared in their study two groups of patients undergoing CABG, the first off-pump and the second with normothermic CPB. The mean CPB time was 69min and the myocardial ischemia time of 34.2 and 35.6 min in groups 1 and 2 respectively. The authors demonstrated that, in patients undergoing CPB, the MDA dosages showed ascending pattern, peaking in the fourth hour after completion of the bypass. In the present study we obtained a bypass time, under hypothermia, similar to previous study (68.1 min.), but with a smaller myocardial ischemia time (19.8 min.). Oxidative stress measured by MDA in the systemic venous return presents ascending pattern between the first and second aortic cross-clamping and without significant reduction until the time A2 (Figure 1). In this study the TBARS levels were not measured after four hours of completion of the bypass, but the downward trend in absolute terms allows us to detect standardization, and not the perpetuation of the ascending pattern as in the study of Matata et al.[19]. When we compare the CS2 and A2 times (Figure 1), we confirmed the downward trend (P<0.05). These differences may be due to the fact that mild hypothermia, as the systemic metabolism attenuation method, may decrease the degree of damage caused by ischemia-reperfusion. Therefore, the use of this technique necessarily affects the early reduction of the levels of malondialdehyde. Regarding the comparisons between the aortic clamping and measured levels of MDA, we observed a greater increase after the second unclamping, especially in the sample of the coronary sinus (CS2) (Figure 1). On the other hand, these concentrations gradually reduce after completion of CPB. This becomes more evident when we compare the TBARS values between CS2 and A2 times, making suppose that the intrinsic myocardial antioxidant mechanisms are more effective in attenuating oxidative stress. Another aspect to be highlighted is the fact that at that time (A2), the completion of CABG allowed restoration of myocardial blood flow before committed by coronary artery disease. The returned circulating therein, allowed mobilizing the ischemic myocardial tissue of all organic antioxidant defenses produced, enabling an early reduction in levels of malondialdehyde. Thus, we note that the myocardial protection methods still deserve extensive discussion, since in most studies that address the ischemia and reperfusion process, it is used as methodology the dosage of injury and myocardial necrosis markers, or that is, restricted only to hypoxia times. Thus, occurring or not the injury mediated by ischemia, reperfusion will trigger additional injury to the already installed, causing

serious cardiac performance changes, often irreversible. In addition, we can also state that the investigations in the field of molecular and atomic biology aim to unravel the metabolic processes in their microstructure, in order to discover methods or subcellular mechanisms allowing them to block or mitigate the myocyte injuries. The lesion detection methodology mediated by reperfusion (TBARS) is still a field to be explored by cardiology. The direct measurement of free radicals is not a feasible procedure because the average extremely short lifetime of these substances. The methodologies used once, such as the measurement of methylene blue does not allow to obtain reliable data due to partial absorption of this compound, which leads to serious errors in determining these radicals. The instrumental methods such as electron paramagnetic resonance are not readily available for this purpose. The method using the measurement of thiobarbituric acid reactive species (TBARS), which was used in this study, is an approximation of the ideal method. However, it is known that the malondialdehyde (MDA) - destruction product of the compounds containing unpaired electrons – is not only the indicator of oxidative stress. It is known that it is only a window on the Universe from free radicals. Nevertheless, for purposes of comparison with the data available in the literature, this approach is acceptable. The intermittent aortic clamping technique is little adopted in the studies presented in the literature. Nevertheless, comparisons with other methods show that intermittent aortic clamping can shorten the lesions mediated by reperfusion. Notwithstanding this, we also evidenced that although the various methods of myocardial protection, oxidative stress always occur. Thus, it is up to the cardiovascular surgeon to investigate new ways, devices or medications that enable the optimization of organic patient’s own defenses against oxidative stress. Thus, it opens up a vast field of research based on molecular and atomic biology, aiming to reduce the injuries of binomial ischemia-reperfusion. CONCLUSION The results of malondialdehyde dosages clearly show that myocardial revascularization with cardiopulmonary bypass is accompanied by elevation of free radicals with this trend to gradually decrease after its completion. The aortic clamping exacerbates the oxidative stress of the coronary sinus venous return when compared to dosages of systemic venous return, but the measurements of coronary effluent presents sharpest decline after reperfusion compared to the systemic metabolism. The behavior of thiobarbituric acid reactive species, despite differences in methodologies, presents similar, indicating that oxidative stress is an unavoidable pathophysiological component.

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Authors’ roles & responsibilities

13. Cherubini A, Riggiero C, Polidori MC, Mecocci P. Potential markers of oxidative stress in stroke. Free Radic Biol Med. 2005; 39(7):841-52.

AEMSASD Analysis and/or interpretation of the data; conception and design; implementation of projects and/or experiments; manuscript writing or critical review of its content PM Analysis and/or interpretation of the data; final approval of the manuscript LZZC Analysis and/or interpretation of the data; final approval of the manuscript

14. Kashyap MK, Yadav V, Sherawat BS, Jain S, Kumari S, Khullar M, et al. Different antioxidant status, total antioxidant power and free radical in essential hypertension. Mol Cell Biochem. 2005;277(1-2):89-99. 15. Lazzarino G, Raatikainen P, Nuutinen M, Nissinen J, Tavazzi B, Di Pierro D, et al. Myocardial release of malondialdehyde and purine compounds during coronary bypass surgery. Circulation. 1994;90(1):291-7.

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16. Marczin N, El-Habashi N, Hoare GS, Bundy RE, Yacoub M. Antioxidants in myocardial ischemia-reperfusion injury: therapeutic potential and basic mechanisms. Arch Biochem Biophys. 2003;420(2):222-36.

2. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edge sword? J Clin Invest. 1985;76(5):1713-9.

17. Percário S, Vital ACC, Jablonka F. Dosagem do malondialdeido. Newslab. 1994;2(6):46-50.

3. Cohen MV. Free radicals in ischemic and reperfusion myocardial injury: is this the time for clinical trials? Ann Intern Med. 1989;111(11):918-31. 4. Bolli R. Oxygen-derived free radicals and myocardial reperfusion injury: an overview. Cardiovasc Drugs Ther. 1991;5 Suppl 2:249-68.

18. Akila, D'souza B, Vishwanath P, D'souza V. Oxidative injury and antioxidants in coronary artery bypass graft surgery: off-pump CABG significantly reduces oxidative stress. Clin Chim Acta. 2007;375(1-2):147-52.

5. Lucchesi BR. Complement, neutrophils and free radicals: mediators of reperfusion injury. Arzneimittelforschung. 1994;44(3A):420-32.

19. Matata BM, Sosnowski AW, Galiñanes M. Off-pump bypass graft operation significantly reduces oxidative stress and inflammation. Ann Thorac Surg. 2000;69(3):785-91.

6. Duilio C, Ambrosio G, Kuppusamy P, DiPaula A, Becker LC, Zweier JL. Neutrophils are primary source of O2 radicals during reperfusion after prolonged myocardial ischemia. Am J Physiol Heart Circ Physiol. 2001;280(6):H2649-57.

20. Melek FE, Baroncini LA, Repka JC, Nascimento CS, Précoma DB. Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation. Rev Bras Cir Cardiovasc. 2012; 27(1):61-5.

7. Vinten-Johansen J. Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovasc Res. 2004;61(3):481-97.

21. Ragab M, Hassan H, Zaytoun T, Refai W, Rocks B, Elsammak M. Evaluation of serum neopterin, high-sensitivity C-reactive protein and thiobarbituric acid reactive substances in Egyptian patients with acute coronary syndromes. Exp Clin Cardiol. 2005;10(4):250-5.

8. Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res. 2004;62(1):74-85.

22. Clermont G, Vergely C, Jazayeri S, Lahet JJ, Goudeau JJ, Lecour S, et al. Systemic free radical activation is a major event involved in myocardial oxidative stress related to cardiopulmonary bypass. Anesthesiology. 2002;96(1):80-7.

9. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003;285(2):H579-88.

23. Consolo LZZ. Alterações plasmáticas do cobre e do zinco em crianças submetidas à cirurgia cardíaca com circulação extracorpórea [Tese de Doutorado]. Campo Grande: Universidade Federal de Mato Grosso do Sul; 2008.

10. Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction (“stunned myocardium”). J Am Coll Cardiol. 1988;12(1):239-49.

24. Milei J, Forcada P, Fraga CG, Grana DR, Iannelli G, Chiariello M, et al. Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion. Cardiovasc Res. 2007;73(4):710-9.

11. Kloner RA, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation. 1989;80(5):1115-27.

25. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis. 2009;204(2):334-41.

12. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem. 2005;12(10):1161-208.

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Lu Q, et al. - Transcatheter valve implantation with balloon-expandable ORIGINALaortic ARTICLE valve: early experience from China

Transcatheter aortic valve implantation with balloonexpandable valve: early experience from China Implantação da válvula aórtica transcateter com válvula balão-expansível: experiência inicial da China

Qingsheng Lu1, MD; Yifei Pei2, MD; Hong Wu2, MD; Zhinong Wang3, MD; Jing Zaiping4, MD, PhD

DOI: 10.5935/1678-9741.20150054

RBCCV 44205-1660

Abstract Objective: The aim of the current study was to evaluate the early experience of the application of transcatheter aortic valve implantation with the balloon-expandable system in China. The transcatheter aortic valve implantation technology has been widely used for patients with inoperable severe aortic stenosis in the developed world. The application of transcatheter aortic valve implantation is still in the early stages of testing in China, particularly for the balloon-expandable valve procedure. Methods: This was a retrospective study. All patients undergoing transcatheter aortic valve implantation with balloon-expandable system in our hospital between 2011 and 2014 were included. Edwards SAPIEN XT Transcatheter Heart Valve was used. The improvement of valve and heart function was evaluated as well as 30-day mortality and major complications according to the VARC-2 definition. Results: A total of 10 transcatheter aortic valve implantation procedures with the balloon-expandable system were performed in our hospital, of which 9 were transfemoral and 1 was transapical. The median age was 76 years, and the median STS score and Logistic EuroSCORE (%) were 8.9 and 16.2. The

implantation was successfully conducted in all patients, only 2 patients had mild paravalvular leak. There was no second valve implantation. Moreover, no 30-day mortality or complications was reported. Following the transcatheter aortic valve implantation procedure, the heart and valve functions had improved significantly. During the follow-up period of 3-34 months, one patient died of lung cancer 13 months after the operation. Conclusion: This early experience has provided preliminary evidence for the safety and efficacy of transcatheter aortic valve implantation procedure with the balloon-expandable system in the developing world with an increasing aging population.

2

Department of Vascular Surgery, Shanghai Changhai Hospital, China. Department of Cardiology, Shanghai Changhai Hospital, China. 3 Department of Cardiothoracic Surgery, Shanghai Changzheng Hospital, China. 4 Professor Shanghai Changhai Hospital, China.

had no role in study design; in the collection, analysis, and interpretation of data; in the manuscript writing; or in the decision to submit the article for publication.

This study was carried out at Shanghai Changhai Hospital, China.

Correspondence address: Jing Zaiping Shanghai Changhai Hospital 168 Changhai Road, Shanghai, 200433, China E-mail: luqingsheng1748@126.com

Descriptors: Aortic Valve Stenosis. Cardiac Catheterization. Heart Valve Diseases. Resumo Objetivo: O objetivo do presente estudo foi avaliar a experiência inicial da aplicação do implante percutâneo da válvula aórtica com o sistema balão-expansível na China. A tecnologia TAVI tem sido amplamente utilizada para pacientes com estenose aórtica

1

Financial support: This study was supported by the 1255 Discipline Construction Program of the Shanghai Changhai Hospital (grant CH12550300), and the Health Care Program of the General Logistics Department of the Chinese People’s Liberation Army (grant 13BJZ30). The funding sources

Article received on March 30th, 2015 Article accepted on August 2nd, 2015

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foi avaliada, bem como mortalidade em 30 dias e as principais complicações de acordo com a definição VARC-2. Resultados: Um total de 10 procedimentos Tavi com o sistema balão-expansível foram realizados em nosso hospital, dos quais 9 foram transfemorais e 1 foi transapical. A idade média foi de 76 anos, e os STS mediana marcar e Logistic EuroSCORE (%) foram de 8,9 e 16,2. A implantação foi realizada com sucesso em todos os pacientes, apenas 2 pacientes tiveram vazamento paravalvar leve. Não houve um futuro implante valvar. Além disso, mortalidade em 30 dias ou complicações não foram relatadas. Seguindo o procedimento de implante percutâneo da válvula aórtica, as válvulas cardíacas e funções melhoraram significativamente. Durante o período de acompanhamento de 3-34 meses, um paciente morreu de câncer de pulmão 13 meses após a operação. Conclusão: Esta experiência inicial apresentou elementos de prova preliminar para a segurança e eficácia do procedimento implante percutâneo da válvula aórtica com o sistema balão-expansível no mundo em desenvolvimento com crescente envelhecimento da população.

Abbreviations, acronyms & symbols AS EOAI LVEF NYHA PARTNER SAVR SD TAVR TTE

TAVI

Aortic stenosis Effective disc mouth area index Left ventricular ejection fraction New York Heart Association Placement of aortic transcatheter valves Surgical aortic valve replacements Standard deviation Transcatheter aortic valve replacement Transthoracic echocardiography

Transcatheter aortic valve implantation

grave inoperável no mundo desenvolvido. A aplicação de implante percutâneo da válvula aórtica está ainda nas etapas iniciais de teste na China, em particular o procedimento de válvula balão-expansível. Métodos: O estudo foi retrospectivo e todos os pacientes submetidos a implante percutâneo da válvula aórtica com sistema balão-expansível em nosso hospital entre 2011 e 2014 foram incluídos. Edwards SAPIEN XT Válvula Cardíaca Transcatheter foi usado. A melhoria do funcionamento da válvula e do coração

Descritores: Estenose da Valva Aórtica. Cateterismo Cardíaco. Doenças das Valvas Cardíacas.

INTRODUCTION

replacement (TAVR) indicated hope for those inoperable or high-risk patients[13,14]. Since 2007, more than 100,000 patients have been treated by TAVR worldwide[15], most of whom were from developed countries. Moreover, a recent meta-analysis estimated that approximately 290,000 elderly patients are TAVR candidates in European countries and North America[16]. Within the 2 widely used device types, the use of balloon-expandable valve (Cribier-Edward) has been shown to have higher success rate than self-expandable valve (CoreValve) in a multi-center study[17]. However, evidence from developing countries was scarce. For example, the initial experience of transcatheter aortic valve implantation (TAVI) was reported in Brazil[18,19], South Africa[20], and India[21], respectively. In mainland China, the use of TAVI did not start until the first successful procedure with self-expandable valve in 2010[22]. The use of balloon-expandable valve remains limited. Since 2011, our hospital was the first to introduce TAVI with the balloon-expandable system in mainland China. The present study aimed to evaluate the early experience of TAVI procedure using balloon-expandable valve in mainland China, and to provide potential evidence for the application and generalization of this novel technology in the developing world with an increasing aging population.

During the past 50 years, the etiology of valvular heart diseases has changed greatly in developed countries, with an increase in non-rheumatic valvular heart diseases such as age-related calcific aortic stenosis (AS)[1,2]. AS is now considered one of the most common valvular diseases in the developed world. For instance, the year-round surgical aortic valve replacements (SAVR) quantity is estimated to be 67,500 in the United States[3]. In China, although limited data indicated that the prevalence of rheumatic heart disease was 10 times higher than developed countries in 2002[4], the rapid growth of an aging population also increases the number of vulnerable age-related AS. Once AS becomes severe and symptomatic, the prognosis is poor with high mortality if left untreated[5,6]. A recent meta-analysis found 69% and 36% of increased risks of cardiovascular and consequential mortality in AS patients, respectively[7], might be partially explained by the selected high risk patients with older age and comorbities. Although the conventional SAVR has excellent outcomes[8-10], it has been reported that patients with severe symptomatic AS had higher mortality when treated by SAVR[11,12]. The emergence and rapid development of transcatheter aortic valve

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METHODS

accurate positioning by aortic root angiograms and TEE guidance, the Transcatheter Heart Valve was deployed during rapid ventricular pacing (Figure 1). Thereafter, the delivery system was retrieved and the femoral access site was percutaneously closed (ProGlideTM, Abbott Vascular, Inc., Abbott Park, IL). For cases that failed to deliver the SAPIEN XT Transcatheter Heart Valve through the femoral access, a transapical approach was conducted through the left ventricular apex. The transpical approacch was previous planned since the patient had severe iliac artery calcification.

Patients This was a retrospective study. All patients that underwent TAVI with the balloon-expandable system in our hospital between 2011 and 2014 were included. All patients were selected by a multidisciplinary core team after extensive screening, including transthoracic echocardiography, coronary arteriography, computed tomographic angiography and lung function examination to evaluate the severity of AS and the existence of any contraindications. Patients that met at least one of the following criteria were included: 1) severe AS with an aortic valve area < 1 cm2; 2) a New York Heart Association (NYHA) functional class II or higher; 3) a STS of 5%~15%; or 4) a Logistic EuroSCORE of 20% or higher. Exclusion criteria included bicuspid aortic valve, acute myocardial infarction, LVEF<20%, aortic valve ring> 25mm or <18mm, severe coronary artery diseases, severe aortic or mitral regurgitation, severe kidney dysfunction, or transient ischemic attack within 6 month. Eligible patients had aortic annulus diameters of 20-25 mm, as determined by the transesophageal echocardiography (TEE). A total of 10 patients (9 male) with NYHA functional class II or higher were included in the current study. Ethics Statement The current study was approved by the Research Ethics Committee of Shanghai Changhai Hospital (CHEC2011099, 9/16/2011) and a waiver of informed consents was granted as the data were retrospectively reviewed and analyzed anonymously. Device and procedure Procedures were performed in hybrid operating room under intratracheal intubation anesthesia. Edwards SAPIEN XT Transcatheter Heart Valve (Edwards Lifescience Corp) was used for all patients (23 and 26 mm). Aortic valve multidetector computed tomography and aorta computed tomography angiography were done before the procedure to evaluate the calcification level. Biplanar TEE was used for real-time supervision during the TAVI procedure. The aortic annulus diameter, aortic valve area, regurgitation velocity, regurgitation gradient, and distance from coronary artery were reevaluated by TEE. A standard transfemoral retrograde approach was applied. In brief, a 18-F eSheath with the introducer (5Fr sheath) was inserted over a 0.035 guidewire into the femoral artery. The 5Fr sheath was advanced over an extra stiff 0.035-inch guide wire (Amplatz, Cook, Inc., Bloomington, IN) into the left ventricle. The 5Fr sheath was then retrieved and the eSheath was introduced to the aortic valve. Following the balloon aortic valvuloplasty under rapid ventricular pacing, the SAPIEN XT Transcatheter Heart Valve delivery system was inserted into the eSheath hub. After

Fig. 1 - Angiography image before (A) and after (B) balloonexpandable valve implantation.

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Outcome measurements The indicators of valve and heart functions including: left ventricular ejection fraction (LVEF, %); aortic annulus diameter (mm); aortic valve area (cm2); effective disc mouth area index (EOAI) and jet velocity (cm/s) were assessed. In regards to the prognosis indicators, the operative (30-day) mortality and major complications including: cerebrovascular accident; arrhythmia; congestive heart failure; myocardial infarction; angina; paravalvular regurgitation; valve migration; valve infection; bleeding; pulmonary infection; urinary system infection; respiratory failure and dialysis-dependent renal failure were evaluated. Outcomes were also evaluated by the VARC II definitions.

Table 1. Baseline and Procedure Characteristics (n=10). Patient Characteristics Baseline Characteristics Age (years)* Gender, male, n (%) Hypertension, yes, n (%) Diabetes, yes, n (%) Coronary artery stenosis, yes, n (%) Surgery history, yes, n (%) Other comorbidities, yes, n (%) Aortic calcification, yes, n (%) Mildly calcified Multiple spots Iliac artery stenosis Femoral artery diameter, yes, n (%) 7.0-8.0 mm 8.1-9.0 mm >9.0 mm NYHA functional class, yes, n (%) I ≼ II Atrioventricular block, yes, n (%) STS score* LVEF (%)* TTE Aortic annulus diameter (mm)* TTE Aortic valve area (cm2)* EOAI* Peak trans aortic gradient (mmHg)* Jet velocity (cm/s)* Logistic EuroSCORE (%)* Procedure Characteristics Procedure time (min)* Blood products (ml)* Length of stay (day)* ICU time (day)* Mild paravalvular leak, yes, n (%) Readmission, yes, n (%)

Statistical analyses Data were presented as median (IQR) for continuous variables, and numbers (%) for categorical variables. The comparison of valve and heart function before and after TVAR were analyzed by Wilcoxon signed-rank test or Fisher’s Exact Test. A P value of P<0.05 was considered statistically significant. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in manuscript writing; or in the decision to submit the article for publication. RESULTS Between 2011 and 2014, a total of 10 patients (9 male) underwent TAVI procedures with the balloon-expandable system in our hospital, of which 9 were transfemoral and 1 was transapical. The baseline and procedure characteristics of patients were presented in Table 1. The median age was 76 (IQR: 75, 78) years. All patients had a NYHA functional class II or higher. Three patients (30%) had atrioventricular block. The median STS score and Logistic EuroSCORE (%) were 8.9 (IQR: 8.1, 11.0) and 16.2 (IQR: 15.5, 17.7), respectively. Following successful implantations with a median procedure time of 200 min, all patients had stable vital signs and were discharged from hospital 4 to 8 days after the TAVI procedure. Only 2 patients (20%) had mild paravalvular leak (Table 1). There was no second valve implantation, valve migration, or infection in any patient. In addition, there was no 30-day mortality or vascular complications according to the VARC-2 definition (Table 2). During the follow-up period of 3-34 months, 1 patient died of lung cancer at 13 months after the TAVI procedure. Following the TAVI procedure, the valve functions were significantly improved (Table 3). The median aortic annulus diameter, aortic valve area and EOAI were significantly increased from 23.0 (IQR: 21.0, 24.0) mm to 26.0 (IQR: 23.0, 26.0) mm, 0.86 (IQR: 0.82, 0.90) cm2 to 1.78 (IQR: 1.72,

76 (75,78) 9 (90.0) 9 (90.0) 2 (20.0) 3 (30.0) 4 (40.0) 2 (20.0) 6 (60.0) 3 (30.0) 1 (10.0) 4 (40.0) 5 (50.0) 1 (10.0) 0 10 (100) 3 (30.0) 8.9 (8.1, 11.0) 62.6 (55.0, 67.0) 23.0 (21.0, 24.0) 0.86 (0.82, 0.90) 0.52 (0.49, 0.53) 104 (88, 117) 510 (456, 542) 16.2 (15.5, 17.7) 200 (185, 255) 200 (0, 800) 7 (6, 8) 0 (0, 1) 2 (20.0) 0 (0)

*Data were presented as median (IQR) for continuous variables. EOAI=effective disc mouth area index; NYHA=New York Heart Association; LVEF=left ventricular ejection fraction; TTE=transthoracic echocardiography

Table 2. The VARC-2 outcomes in the 30-day follow up period. Outcomes All-cause mortality Cardiac mortality Stroke Life-threatening bleeding Acute kidney injury, stage 2 or 3 Coronary artery obstruction Major vascular complication Valve-related dysfunction requiring repeat procedure

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Table 3. Comparison of valve and heart function before and after TAVI. Baseline Characteristics LVEF (%) TTE Aortic annulus diameter (mm) TTE Aortic valve area (cm2) EOAI Jet velocity (cm/s) NYHA functional class ≼ II, yes, n (%)

Before TAVI 62.6 (55.0, 67.0) 23.0 (21.0, 24.0) 0.86 (0.82, 0.90) 0.52 (0.49, 0.53) 510 (456, 542) 10 (100)

After TAVI 64.5 (61.0, 67.0) 26.0 (23.0, 26.0) 1.78 (1.72, 1.80) 1.06 (1.01, 1.12) 205 (186, 236) 2 (20)

P value 0.43 0.021 <0.001 <0.001 <0.001 <0.001

Data were presented as median (IQR) or n (%). EOAI=effective disc mouth area index; NYHA=New York Heart Association; LVEF=left ventricular ejection fraction; TTE=transthoracic echocardiography

1.80) cm2 and 0.52 (IQR: 0.49, 0.53) to 1.06 (IQR: 1.01, 1.12), respectively (all P<0.05). In addition, the median jet velocity decreased from 510 (IQR: 456, 542) to 205 (IQR: 186, 236) cm/s (P<0.001). Meanwhile, the NYHA functional class of 8 patients (80%) had improved to class I within 30 days in the postoperative period.

toms was also lower in the TAVR group compared with the standard therapy group (25.2% vs 58.0%, respectively)[30]. In the PARTNER A trial, the TAVR and SAVR procedure had comparable mortality and symptom improvement for high-risk surgical candidates during the 2-year follow-up period[31,32]. However, evidence from developing countries including China remains limited. Mortality, as well as major complications such as cerebrovascular accident, paravalvular regurgitation, and vascular events, are concerning implications for the use of the TAVR procedure. In the TAVR group of the PARTNER A trial, the 30-day mortality, major cerebrovascular accident, and major vascular complications were 3.4%, 3.8% and 11.0%, respectively[31], whilst the all-cause mortality 2 years after the TAVR procedure was 33.9%[32]. Moreover, among all eligible TAVR cases utilizing the Sapien Transcatheter Heart Valve from November 2011 to May 2013 in the United States, the in-hospital mortality and cerebrovascular accident rates were 5.5% and 2.0%, respectively[33]. In contrast, in the present study, there were zero cases of mortality and major complications in the 30-day follow-up period and only one patient died of lung cancer 13 months after the TAVR procedure during the follow-up period. Although a decisive conclusion of low mortality and complication rate could not be made based on the findings of the current study, the extensive screening and careful evaluation for all patients by a multidisciplinary core team before TAVR procedure may have contributed to the higher success rate and better prognosis. In addition, in terms of the incorporation of TAVR in clinical practice, functional improvement would provide valuable information. A systematic review of current reports revealed consistent benefits of TAVR by the improvement in NYHA functional class[34]. In the current study, improvement in heart and valve function after TAVI was also observed. Studies with a larger number of cases and a longer follow-up period are required to validate the findings of the current study. Currently, the TAVR approach has been widely utilized in developed countries. The application of TAVR

DISCUSSION According to the China Report of the Development on Aging Cause, the percentage of the aging population in China was 14.8% (more than 0.2 billion) in 2013[23]. The rapid growth of an aging population has resulted in a significant challenge in defending age-related chronic diseases, such as calcific AS. Due to poor prognosis after the manifestation of cardiovascular symptoms, safe and effective medical procedures are in urgent need to treat AS, particularly for those elderly inoperable patients. Our hospital was the first to introduce TAVI with the balloon-expandable system in mainland China. Our early experiences with favorable improvement of heart and valve function has provided preliminary evidence for the safety and efficacy of the TAVI procedure in severe AS patients in mainland China. Although conventional SAVR has excellent outcomes[8-10], the mortality and morbidity rates remain high in patients at extreme high-risk or inoperable patients with severe AS[11,12]. The emergence of TAVR technology offers a novel, less-invasive approach with a success procedure rate of over 93%[24-26]. The advantages of TAVR procedure have been evaluated thoroughly in developed counties, especially from large-scale studies of registry data from US and European countries including more than 10,000 patients[27-29]. Moreover, according to the findings from the Placement of Aortic Transcatheter Valves (PARTNER) B trial, inoperable patients that underwent TAVR had significantly lower 1-year mortality rate compared with those patients that underwent standard therapy (30.7% vs. 50.7%, respectively). Among the survivors, the 1-year rate of cardiac symp-

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is, however still in the very early stages in developing countries such as China, due to high-demand technology and expensive therapeutic fees. Whilst previous reports have shown favorable outcomes of the TAVR procedure in inoperable or high-risk patients with severe AS, the generalization of TAVR in routine therapy remains complex, including the accessibility of a facility for this procedure in a clinical center, the experience of the operator and the core team, the selection and evaluation of high-risk patients, the procedure performance, and perioperative and postoperative care. Furthermore, whilst rapid incorporation of the TAVR procedure in clinical treatment is progressing, technical challenges remain[15]. In the PARTNER A trial, among patients that have undergone TAVR, there was increased paravalvular regurgitation and major vascular complications than those patients treated by SAVR[31,32]. In the PARTNER B trial, there was also a higher incidence of major cerebrovascular accident and major vascular events in the TAVR group compared with the standard therapy group[30]. In contrast, the considerably advanced technology in the SAVR procedure has greatly improved the surgical results in high-risk patients[35]. To avoid the misuse of TAVR, the ACCF/AATS/SCAI/STS expert consensus published in 2012, has provided standards for applying TAVR in the clinical practice in the United States[5]. However, whether these standards derived from Western populations, can be applied or not in China, remain unknown. Moreover, whether the commercially available Transcatheter Heart Valve designed for Western patients will fit Chinese patients needs to be elucidated in large multicenter studies with longer follow-up duration.

ACKNOWLEDGEMENTS This study was supported by the 1255 Discipline Construction Program of the Shanghai Changhai Hospital (grant CH12550300), and the Health Care Program of the General Logistics Department of the Chinese People’s Liberation Army (grant 13BJZ30). The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the manuscript writing; or in the decision to submit the article for publication. All authors confirmed that we had full control of the design and methods of the study, the data analysis and production of the written report. Authors’ roles & responsibilities QL

YP HW ZW JZ

Strength and Limitations To the best of our knowledge, the current study was the first attempt to evaluate the TAVI approach with the balloon-expandable system in mainland China. This study contains several limitations. The number of patients that underwent the TAVI procedure with the balloon-expandable system was very small, due to the demanding technology and high expenditure of this procedure. Secondly, the current study was a single center study. Due to the complexity of incorporating TAVI in clinical practice, the results of the current study may not be generalized to other centers in China.

Analysis and/or interpretation of data; statistical analysis; final manuscript approval; implementation of projects and or experiments; manuscript writing or critical review of its content Final manuscript approval; implementation of projects and/ or experiments; manuscript writing or critical review of its content Final manuscript approval; implementation of projects and/ or experiments; manuscript writing or critical review of its content Final manuscript approval; implementation of projects and/ or experiments; manuscript writing or critical review of its content Final manuscript approval; study design; implementation of projects and/or experiments; manuscript writing or critical review of its content

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CONCLUSION

4. Zhimin W, Yubao Z, Lei S, Xianliang Z, Wei Z, Li S, et al. Prevalence of chronic rheumatic heart disease in Chinese adults. Int J Cardiol. 2006;107(3):356-9.

In conclusion, the current study has provided an evaluation of early experience in the application of TAVI procedure with the balloon-expandable system in mainland China. Further clinical evidence and longer follow-up duration are required to further explore the clinical value and general possibility of introducing TAVI procedure in the developing world with an increasing aging population.

5. Holmes DR Jr, Mack MJ, Kaul S, Agnihotri A, Alexander KP, Bailey SR, et al. 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement. J Am Coll Cardiol. 2012;59(13):1200-54.

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6. Ben-Dor I, Pichard AD, Gonzalez MA, Weissman G, Li Y, Goldstein SA, et al. Correlates and causes of death in patients with severe symptomatic aortic stenosis who are not eligible to participate in a clinical trial of transcatheter aortic valve implantation. Circulation. 2010;122(11 Suppl):S37-42.

transcatheter aortic valve replacement: the CHOICE randomized clinical trial. JAMA. 2014;311(15):1503-14. 18. Pontes JC, Duarte JJ, Silva AD, Gardenal N, Dias AM, Benfatti RA, et al. Initial and pioneer experience of transcatheter aortic valve implantation (Inovare) through femoral or iliac artery. Rev Bras Cir Cardiovasc. 2013;28(2):208-16.

7. Coffey S, Cox B, Williams MJ. The prevalence, incidence, progression, and risks of aortic valve sclerosis: a systematic review and meta-analysis. J Am Coll Cardiol. 2014;63(25 Pt A):2852-61.

19. Gaia DF, Palma JH, Ferreira CB, Souza JA, Agreli G, Guilhen JC, et al. Transapical aortic valve implantation: results of a Brazilian prosthesis. Rev Bras Cir Cardiovasc. 2010;25(3):293-302.

8. Schwarz F, Baumann P, Manthey J, Hoffmann M, Schuler G, Mehmel HC, et al. The effect of aortic valve replacement on survival. Circulation. 1982;66(5):1105-10.

20. Mabin TA, Condolfi P. An analysis of real-world cost-effectiveness of TAVI in South Africa. Cardiovasc J Afr. 2014;25(1):21-6.

9. Murphy ES, Lawson RM, Starr A, Rahimtoola SH. Severe aortic stenosis in patients 60 years of age or older: left ventricular function and 10-year survival after valve replacement. Circulation. 1981;64(2 Pt 2):II184-8.

21. Maqbool S, Kumar V, Rastogi V, Seth A. Transcatheter aortic valve implantation under conscious sedation - the first Indian experience. Indian Heart J. 2014;66(2):208-10. 22. Ge J, Zhou D, Pan W, Wang Z, Ge L, Pan C, et al. Initial experience of percutaneous aortic valve replacement in China. Chin J Intervent Cardiol. 2010;8:243-56.

10. Pei HJ, Wu YJ, Yang YJ, Xu B, Chen JL, Qiao SB, et al. Current treatment status in patients with severe aortic valve stenosis and outcome of long term follow-up at advanced age: a Chinese single center study. Chin Med J (Engl). 2011;124(18):2879-82.

23. Wu Y. China report of the development on aging cause (2013). Beijing: Social Sciences Academic Press; 2013.

11. Bakaeen FG, Chu D, Huh J, Carabello BA. Is an age of 80 years or greater an important predictor of short-term outcomes of isolated aortic valve replacement in veterans? Ann Thorac Surg. 2010;90(3):769-74.

24. Grube E, Naber C, Abizaid A, Sousa E, Mendiz O, Lemos P, et al. Feasibility of transcatheter aortic valve implantation without balloon pre-dilation: a pilot study. JACC Cardiovasc Interv. 2011;4(7):751-7.

12. Thourani VH, Ailawadi G, Szeto WY, Dewey TM, Guyton RA, Mack MJ, et al. Outcomes of surgical aortic valve replacement in high-risk patients: a multiinstitutional study. Ann Thorac Surg. 2011;91(1):49-55.

25. Thomas M, Schymik G, Walther T, Himbert D, Lefèvre T, Treede H, et al. Thirty-day results of the SAPIEN aortic Bioprosthesis European Outcome (SOURCE) Registry: a European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve. Circulation. 2010;122(1):62-9.

13. Andersen HR, Knudsen LL, Hasenkam JM. Transluminal implantation of artificial heart valves. Description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. Eur Heart J. 1992;13(5):704-8.

26. Rodés-Cabau J, Webb JG, Cheung A, Ye J, Dumont E, Feindel CM, et al. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience. J Am Coll Cardiol. 2010;55(11):1080-90.

14. Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106(24):3006-8. 15. Leon MB, Gada H, Fontana GP. Challenges and future opportunities for transcatheter aortic valve therapy. Prog Cardiovasc Dis. 2014;56(6):635-45.

27. Holmes DR Jr, Brennan JM, Rumsfeld JS, Dai D, O’Brien SM, Vemulapalli S, et al; STS/ACC TVT Registry. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA. 2015;313(10):1019-28.

16. Osnabrugge RL, Mylotte D, Head SJ, Van Mieghem NM, Nkomo VT, LeReun CM, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013;62(11):1002-12.

28. Walther T, Hamm CW, Schuler G, Berkowitsch A, Kötting J, Mangner N, et al; GARY Executive Board. Perioperative results and complications in 15,964 transcatheter aortic valve replacements: prospective data from the GARY Registry. J Am Coll Cardiol. 2015;65(20):2173-80.

17. Abdel-Wahab M, Mehilli J, Frerker C, Neumann FJ, Kurz T, Tölg R, et al; CHOICE investigators. Comparison of balloonexpandable vs self-expandable valves in patients undergoing

29. Duncan A, Ludman P, Banya W, Cunningham D, Marlee D, Davies S, et al. Long-term outcomes after transcatheter aortic valve replacement in high-risk patients with severe aortic stenosis:

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the U.K. Transcatheter Aortic Valve Implantation Registry. JACC Cardiovasc Interv. 2015;8(5):645-53.

outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012;366(18):1686-95.

30. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, et al; PARTNER Trial Investigators. Transcatheter aorticvalve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597-607.

33. Mack MJ, Brennan JM, Brindis R, Carroll J, Edwards F, Grover F, et al. Outcomes following transcatheter aortic valve replacement in the United States. JAMA. 2013;310(19):2069-77. 34. Kim CA, Rasania SP, Afilalo J, Popma JJ, Lipsitz LA, Kim DH. Functional status and quality of life after transcatheter aortic valve replacement: a systematic review. Ann Intern Med. 2014;160(4):243-54.

31. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, et al; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-98.

35. Bajona P, Suri RM, Greason KL, Schaff HV. Outcomes of surgical aortic valve replacement: the benchmark for percutaneous therapies. Prog Cardiovasc Dis. 2014;56(6):619-24.

32. Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, et al; PARTNER Trial Investigators. Two-year

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Pereira SN, etORIGINAL al. - Comparison of two technics of cardiopulmonary bypass ARTICLE (conventional and mini CPB) in the trans- and postoperative periods of cardiac surgery

Comparison of two technics of cardiopulmonary bypass (conventional and mini CPB) in the trans- and postoperative periods of cardiac surgery Comparação de duas técnicas de circulação extracorpórea (convencional e mini CEC), nos períodos trans e pós-operatório de cirurgia cardíaca

Sergio Nunes Pereira1, MD, PhD; Izabelle Balta Zumba2; Micheline Sulzbacher Batista2; Daniela Da Pieve2; Elisandra dos Santos2, MSc, PhD; Ralf Stuermer3, MD; Gerson Pereira de Oliveira3, MD; Roberta Senger3

DOI: 10.5935/1678-9741.20150046

RBCCV 44205-1661

Abstract Objective: This study aimed to compare the effects of two different perfusion techniques: conventional cardiopulmonary bypass and miniature cardiopulmonary bypass in patients undergoing cardiac surgery at the University Hospital of Santa Maria - RS. Methods: We perform a retrospective, cross-sectional study, based on data collected from the patients operated between 2010 and 2013. We analyzed the records of 242 patients divided into two groups: Group I: 149 patients undergoing cardiopulmonary bypass and Group II - 93 patients undergoing the miniature cardiopulmonary bypass. Results: The clinical profile of patients in the preoperative period was similar in the cardiopulmonary bypass and miniature cardiopulmonary bypass groups without significant differences, except in age, which was greater in the miniature cardiopulmonary bypass group. The perioperative data were significant of blood collected for autotransfusion, which were

higher in the group with miniature cardiopulmonary bypass than the cardiopulmonary bypass and in transfusion of packed red blood cells, which was higher in cardiopulmonary bypass than in miniature cardiopulmonary bypass. In the immediate, first and second postoperative period the values of hematocrit and hemoglobin were higher and significant in miniature cardiopulmonary bypass than in the cardiopulmonary bypass, although the bleeding in the first and second postoperative days was higher and significant in miniature cardiopulmonary bypass than in the cardiopulmonary bypass. Conclusion: The present results suggest that the miniature cardiopulmonary bypass was beneficial in reducing the red blood cell transfusion during surgery and showed slight but significant increase in hematocrit and hemoglobin in the postoperative period.

Centro de Ciências da Saúde da Universidade Federal de Santa Maria (CCS – UFSM), Santa Maria, RS, Brazil. 2 Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil. 3 Hospital Universitário de Santa Maria (HUSM), Santa Maria, RS, Brazil.

Correspondence address: Sergio Nunes Pereira Universidade Federal de Santa Maria Av. Roraima, 1000 – Camobi - Santa Maria, RS, Brazil Zip code: 97105-900 E-mail: sergio.nunespereira@gmail.com

Descriptores: Cardiopulmonary Bypass. Perfusion. Postoperative Period.

1

This study was carried out at Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil, and Hospital Universitário de Santa Maria (HUSM), Santa Maria, RS, Brazil.

Article received on February 17th, 2015 Article accepted on June 23rd, 2015

Financial Support: Hospital Universitário de Santa Maria.

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Resultados: O perfil clínico dos pacientes no pré-operatório foi semelhante nos grupos circulação extracorpórea e minicirculação extracorpórea sem diferenças significativas, exceto na idade, maior no grupo minicirculação extracorpórea. Os dados perioperatórios foram significativos de sangue coletadas para autotransfusão, que foram maiores no grupo com minicirculação extracorpórea do que a circulação extracorpórea e na transfusão de concentrado de hemácias, superior em circulação extracorpórea do que em minicirculação extracorpórea. Nos valores pós-operatório imediato, primeiro e segundo, os níveis de hematócrito e da hemoglobina foram maiores e significativos na minicirculação extracorpórea que no circulação extracorpórea, embora o sangramento no primeiro e segundo dias pós-operatórios tenha sido maior e significativo no minicirculação extracorpórea que no circulação extracorpórea. Conclusão: Os resultados sugerem que a minicirculação extracorpórea foi benéfica em reduzir a transfusão de células vermelhas do sangue durante a cirurgia e houve discreta, mas significativa, elevação do hematócrito e hemoglobina no pós-operatório.

Abbreviations, acronyms & symbols 1st POP 2nd POP ACT CABG CPB IOPP MCPB SIRS

First postoperative day Second postoperative day Activated coagulation time Coronary artery bypass grafting Cardiopulmonary bypass Immediate postoperative period Miniature cardiopulmonary bypass Systemic inflammatory response syndrome

Resumo Objetivo: Este estudo teve como objetivo comparar os efeitos de duas técnicas de perfusão diferentes: convencional (CEC) e mini (MCEC) em pacientes submetidos à cirurgia cardíaca no Hospital Universitário de Santa Maria - RS. Métodos: Foi realizado um estudo retrospectivo, transversal, baseado em dados coletados dos pacientes operados entre 2010 e 2013. Foram analisados os ​​ registros de 242 pacientes divididos em dois grupos: Grupo I - 149 pacientes submetidos à circulação extracorpórea e Grupo II - 93 pacientes submetidos à minicirculação extracorpórea.

Descritores: Circulação extracorpórea. Perfusão. Período pós-operatório.

INTRODUCTION

other surgeons[17-20], with good results in relation to the CPB. But these technical limitations were reported as difficult as revascularization of the lower wall of the left ventricle, large cardiomegaly and severe heart failure. In these situations, the technique often resulted in incomplete revascularization[21]. Another option found to the problems of CPB was to minimize the volume of the infusion, with the miniaturization of the cardiopulmonary bypass (MCPB). Afterwards, several studies published comparing the CPB with off pump surgery and the MCPB, finding lower presence of hemodilution, coagulopathy[21] need for transfusion of red blood cells[22-27] and lower systemic inflammatory reaction in the surgery without CPB and MCPB in relation to the CPB[28]. It was also observed higher hemoglobin levels in MCPB than in CPB[26]. When comparing off-pump surgery and MCPB, the following effects were described: similar level of inflammatory response[25], but more controlled surgical field[21], better coronary artery bypass grafting (CABG)[25] and higher level of hemoglobin in the MCPB than in off-pump. Other authors considered not significant the difference between CPB and the MCPB for bleeding, renal injury, length of stay[29] and evolution of low-risk patients[30]. In our Service, at the University Hospital of Santa Maria, from 2010, we began using MCPB in CABG surgery. In 2011, we added to this technique an autotransfusion equipment with hemoconcentration. This year, a resident of anesthesia and Master’s student, comparing patients undergoing coronary artery bypass surgery found

Cardiac surgery had major limitations in the beginning, in the early twentieth century, for not being able to stop and open the heart to treat intracardiac lesions. However, from the development of an artificial heart-lung machine[1], showed great progress, especially with the development of cardiopulmonary bypass, progressively improved until 1954, when its use in humans has started[2]. Since that time this technique has become widespread worldwide and known as the largest contribution to cardiac surgery and cardiology for the world[3-5]. In Brazil this technique started in 1955[6-7], followed by several surgeons[8-12], which put the country in an international leading position in cardiovascular surgery with important contributions to the development and improvement of perfusion. However, with the method came the challenges to circulate blood into metal and plastic surfaces. The contact of blood with this surfaces predisposes to changes in blood components, such as red cells, white cells, platelets, and plasma lipoproteins, that can suffer degradation and partial destruction of these elements, resulting in anemia and tissue inflammatory reactions as the systemic inflammatory response syndrome (SIRS)[13], need for transfusion with homologous red blood cells[14] and increased risk of postoperative infection[15]. Because of this situation, various techniques were used, such as coronary artery bypass grafting without cardiopulmonary bypass (CPB) in 1955[16], and later with

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less need and lower volume of packed red blood cells in the autotransfusion group than in those without its use[28]. Based on this initial experience, we decided to perform a retrospective analysis with a review of medical records of patients undergoing consecutive cardiac surgeries in 2010 to 2013 period, regarding the effects of two types of cardiopulmonary bypass: (with conventional CPB and MCPB) on the results of clinical and laboratory parameters of the periods before, during and after surgery. Considering the fact that this study was retrospective, we analyzed mainly the clinical aspects and changes in the hemoglobin, hematocrit, platelets, complications related to bleeding and the need of red blood pack transfusion during surgery and in the postoperative period.

tive period (POI) between arrival at the Intensive Cardiology Unit (ICU) and 6:00 pm the following day, and then the first postoperative day (24 h after) and the second PO (48 h after). In this study we analyzed the medical records of 242 patients who underwent surgery between 2010-2013, divided into two groups: Group I (GI) - 149 patients undergoing surgery with conventional cardiopulmonary bypass (CPB). Group II (GII) - 93 patients who underwent surgery with miniaturized cardiopulmonary bypass (MCPB). The patients in GI underwent surgery with machine and conventional CPB circuits (Braile Biomédica®) and centrifugal pump (Maquet®). The GII, were operated circuit, centrifugal pump and MCPB Maquet® machine (Figure 1). Auto transfusion was performed by using a device named Autolog (Medtronic®) (Figure 2), when deemed necessary by the surgeon. The surgical procedures were performed by the usual techniques, corresponding to each system. Autolog® was used in both types of perfusion: 148 in the CPB group and 88 in the MCPB group. Data were tabulated in spreadsheet (Excel 2010 Windows®), and analyzed using the statistical package (SPSS 15.0)®, with test application T Student for parameters with normal distribution and Mann Whitney test for abnormal distribution, considering the significance of P<0.05. Inclusion criteria were cardiac surgeries performed sequentially in the period 2010-2013, and the exclusion were emergency surgery, reoperation and complex surgeries such as aneurysms and aortic dissection, given that our initial aim was to compare these perfusion techniques in routine surgery.

METHODS Ethical considerations This study was reviewed and approved by the Research Ethics Committee of the Federal University of Santa Maria, RS, with number CAAE: 21598213.1.0000.5346 and order number: 434.030. Date: 08/10/2013. Data were collected in chips (Chart 1), whose items refer to clinical, surgical and laboratory parameters of the pre-, intra- and postoperative surgery, with emphasis on hematological aspects, bleeding and transfusions, regarding the patients underwent conventional CPB and MCPB. The preoperative data refer to clinical and laboratory parameters collected before surgery; the perioperative are related to the period from the beginning to the end of surgery. The postoperative period was subdivided into three sub-periods: the early postopera-

Chart I. Cardiac surgery sheet data of pre-, trans- and postoperative periods. Hospital Records SAH

Name

Age

Sex

Weight

BMI

COPD

Dislipidemia

Renal Insuff.

Previous AMI

Other

LITA

B. S.

C.T.

Time ECC

End Ht

PRBC_Top

B. B.

End ACT

End Ht

1st and 2nd POP Bleed.

1st and 2nd POP Ht

1st and 2nd POP Hb

IP Plat.

Body Surface Cir. Date

Smoking

DM_2

Type of Surgery

Type ECC

Pre Plat.

Initial ACT

Top Bleeding

Autol. Transf.

End Hb

IP Bleed.

IP Ht

IP Hb

IP CHAD.

1st and 2nd POP Plat.

Hosp. Dis.

Obs: Complication

BMI=body mass index; BS=body surface; DM 2= diabetes mellitus type 2; SAH=Hypertension; COPD=chronic obstructive pulmonary disease; Dyslipid=dyslipidemia; Renal F=renal failure; AMI=acute myocardial infarction; EF=ejection fraction; LITA=left internal thoracic artery; CABG=coronary artery bypass surgery; Clamp T=clamp time; Init Ht=initial hematocrit; Init Hb= initial haemoglobin; Pre Plat=previous platelets; Init ACT=activated clotting time; IP Bleed=intraoperative bleeding; Autol Tr=autologous transfusion; CRBC=concentrate of red blood cells; Blood Bal=blood balance; ACT: activated clotting time; Final Ht=final Hematocrit; Final Hb=final hemoglobin; Final Plat=final platelets; IPO bleed.=Bleeding pf immediate postoperative bleeding; IPO Ht=immediate postoperative hematocrit; IPO Hb=immediate postoperative hemoglobin; IPO CRBC= immediately postoperative CRBC; IPO Plat=Immediate postoperative period platelets; Bleed 1st and 2nd PO=Bleeding on the 1st and 2nd postoperative day; Ht 1st and 2nd PO=hematocrit on the 1st and 2nd postoperative day; Hb 1st and 2nd PO=hemoglobin on the 1st and 2nd postoperative day; Plat 1st and 2nd PO=Platelets on the 1st and 2nd postoperative day

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Table 1. Preoperative clinical and anthropometric parameters in CPB and MCPB groups. Nominal variables Gender Female Male Smoking Ex No Yes DM No Yes SAH No Yes COPD No Yes Dyslipidemia No Yes Renal Failure No Yes Previous AMI No Yes

Fig. 1 - Maquet set consisting of mini bypass circuit connected to the centrifugal pump and the extracorporeal circulation machine.

Numeric variables AGE BMI Body Surface EF

P Value

G I (CPB) N (%)

G II (MCPB) N (%)

45 (30.2%) 104 (69.8%)

27 (29.0%) 66 (71.0%)

0.85

66 (44.6%) 52 (35.1%) 30 (20.3%)

45 (48.9%) 25 (27.2%) 22 (23.9%)

0.43

96 (64.9%) 52 (35.1%)

55 (59.1%) 38 (40.9%)

0.37

21 (14.1%) 128 (85.9%)

14 (15.1%) 79 (84.9%)

0.84

131 (87.9%) 18 (12.1%)

83 (89.2%) 10 (10.8%)

0.75

43 (28.9%) 106 (71.1%)

22 (23.9%) 70 (76.1%)

0.40

139 (93.3%) 10 (6.7%)

84 (90.3%) 9 (9.7%)

0.40

84 (57.1%) 63 (42.9%) CPB

46 (49.5%) 47 (50.5%) MCPB

MEAN (± SD) 59.21 (11.63) 26.73 (3.91) 1.83 (0.24) 62.11 (10.71)

MEAN (± SD) 62.51 (9.55) 26.91 (4.81) 1.85 (0.18) 59.37 (13.27)

0.25

P-value 0.04* 0.80 0.79 0.20

*P≤0.05. CPB=cardiopulmonary bypass; MCPB=mini cardiopulmonary bypass; DM=diabetes mellitus; SAH=Hypertension; COPD=chronic obstructive pulmonary disease; AMI=acute myocardial infarction; BMI=body mass index; EF=ejection fraction; SD=standard deviation

Fig. 2 - Bypass set with centrifugal pump coupled with the module of auto transfusion (Autolog).

RESULTS

The immediate postoperative period (Table 3), with discrete higher values of hematocrit and hemoglobin in the mini CPB than in CPB (Figures 4 and 5), respectively, with significant differences (P<0.05). In the first and second postoperative period bleeding was also observed (Figure 6) and most significant in the mini CPB in relation to the CPB (P<0.05), however, despite this, the hematocrit and hemoglobin levels remained higher in mini CPB than in the CPB, with subtle differences, but significant (P<0.05). The complication about SIRS where referred in the Introduction, in the historic context of one important event that is related to CPB. However, in this study, we referred only the complications related to bleeding, need of RBC transfusion and change of erythrocytes, hematocrit, hemoglobin and platelets during surgery and postoperative period (Figure 7).

The results were tabulated according to the analysis period: preoperative (Table 1), intraoperative (Table 2) and postoperative (Table 3). The clinical profile of patients preoperatively (Table 1) was similar in groups I (CPB) and II (mini CPB), differing only in age, the greater the mini CPB in relation to the CPB. (P<0.05). During the surgery (Table 2) there was no significant difference in duration of CPB and laboratory parameters and bleeding. There were significant differences in the collection of red blood cells for autologous transfusion (P<0.05) in the mini CPB in relation to the CPB and the volume of transfused red blood cells concentrate (Figure 3) was greater and significant in the CPB regarding the mini pump group (P<0.04).

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Table 2. Parameters of perioperative period. Parameters CPB TIME Initial Ht. Initial Hb Initial Platelets Initial ACT Trans op bleeding Autol transf PO Packed red blood cells Final ACT Final Ht Final Hb Final Platelets

G I (CPB) Mean (± SD) 149 94.06 (±25.85) 149 37.52 (±5.74) 149 12.95 (±2.08) 146 219438.36 (±63383.341) 148 150.52 (±68.71) 132 556.39 (±449.39) 148 184.45 (±265.88) 147 106.37 (±211.969) 149 144.69 (±50.01) 149 27.82 (±5.53) 149 10.11 (±2.13) 148 167154.73 (±61929.863)

G II (MCPB) Mean (± SD) 93 89.95 (±23.62) 93 37.24 (±5.10) 93 12.74 (±1.83) 93 207249.76 (±58345.379) 92 150.59 (±85.21) 75 603.16 (±501.36) 88 274.80 (±345.97) 82 49.13 (±133.292) 93 143.60 (±63.32) 93 29.22 (±5.87) 93 10.37 (±1.91) 87 168678.16 (±60660.798)

%

P value

-4.37

0.29

-0.75

0.69

-1.62

0.41

-5.55

0.16

0.05

0.63

8.41

0.77

48.98

0.05*

-53.81

0.04*

-0.75

0.21

5.03

0.06

2.57

0.12

0.91

0.95

* P≤0.05. ACT=activated coagulation time; CPB=cardiopulmonary bypass; MCPB=mini cardiopulmonary bypass; SD=standard deviation; Hb=hemoglobin; Ht=hematocrit; Autol Tranf=autologous transfusion

Fig. 3 – Comparison of the type of infusion and compared to autologous transfusion concentrated red blood cell. *P<0.05; mini CPB=miniaturized cardiopulmonary bypass.

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Table 3. Parameters of postoperative period. Parameters

G I (CPB) Mean (± SD) 149 IPO Bleeding 325.10 (±312.52) 146 Ht IPO 32.14 (±5.28) 145 IPO Hb 10.73 (±1.71) 147 IPO Packed red blood cell 143.88 (±278.16) 142 IPO Platelets 162756.34 (±57825.240) 149 1st PO Bleeding 518.15 (±363.39) 149 1st PO Ht 30.43 (±5.0283) 149 1st PO Hb 10.162 (±1.4594) 149 2nd PO Bleeding 254.56 (±318.48) 148 2nd PO Ht 27.326 (±4.2496) 149 2nd PO Hb 9.053 (±1.38) 149 1st PO Platelets 177234.90 (±172925.323) 148 2nd PO Platelets 152662.16 (±143563.992)

G II (MCPB) Mean (± SD) 90 278.67 (±188.07) 92 33.726 (±4.70) 92 11.22 (±1.57) 93 96.51 (±198.94) 91 159538.46 (±54.421.260) 91 582.20 (±343.93)* 93 31.979 (±4.2382)* 93 10.537 (±1.4544)* 86 306.22 (±289.22)* 93 28.488 (±4.1622)* 93 9.406 (±1.39) 93 188053.76 (±267024.765) 93 134741.94 (±50825.127)

%

P Value

-14.28

0.84

4.93

0.03*

4.57

0.03*

-32.92

0.30

-1.98

0.73

12.36

0.04*

5.09

0.04*

3.69

0.05*

20.29

0.02*

4.25

0.04*

3.90

0.05*

6.10

0.83

-11.74

0.67

*P≤=0.05. CPB=cardiopulmonary bypass; MCPB=mini cardiopulmonary bypass; Hb=hemoglobin; Ht=hematocrit; IPO=immediate postoperative; PO=perioperative; SD=standard deviation

Fig. 4 – Hematocrit before, during, and after surgery. *P<0.05; Init Ht=initial hematocrit; Final Ht=final hematocrit; Ht POI=hematocrit on the immediate postoperative period; Ht 1 PO= hematocrit on the first day after surgery; Ht 2 PO= hematocrit on the second day after surgery.

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Fig. 5 – Hemoglobin before, during, and after surgery. *P<0.05; Init Heb=initial hemoglobin; Final Hb=final hemoglobin; Hb POI=hemoglobin on the immediate postoperative period; Heb 1 PO=hemoglobin on the first day after surgery; Heb 2 PO=hemoglobin on the second day after surgery.

Fig. 6 – Bleeding trends in the trans- and postoperative periods. *P<0.05; Bleed T.Op=postoperative bleeding; Bleed POI=bleeding on the immediate postoperative period; Bleed. 1o PO=bleeding on the first day after surgery; Bleed. 2o PO=bleeding on the second day after surgery.

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Fig. 7 – Evolution of platelets, during, and after surgery. *P>0.05; Pre Plat=previous platelets; Final Plat=final platelets; Plat POI=platelets on the postoperative period; Plat. 1o PO=platelets on the first day after surgery; Plat. 2o PO =platelets on the second day after surgery.

DISCUSSION

with the exception of age, with a slight but significant increase in the group with mini CPB compared to conventional CPB (P<0.05). These findings are consistent with those of other authors[25,26]. In the perioperative period the volume of blood collected autotransfusion: 274.80 (±345.97) was 48.98% higher and significant (P<0.05) in the group with mini CPB in relation to the CPB: 184.45 (±265.88), but the average volume of transfused red blood cells was 106,37 ml (±211.97) in the pump group and 49.13 ml (±133.29) in the mini-pump group, with a difference of 57.24 ml (-53.81%) of this in relation to the CPB (P<0.04), showing a favorable effect on the mini CPB in relation to the CPB. These findings suggest that patients of mini CPB, being autotransfused during surgery had less need for homologous blood transfusion than CPB. This result was similar to the data of other authors who found mean values of homologous blood units of 0.8 unit/patient in the groups with mini pump and off-pump, and 1.8 unit/patient in the CPB[25]. Another study showed that there was significant reduction in the volume of blood transfusion: 0.53±0.90 CH unit in mini CPB and 1.3±1.93 units in the CPB (P<0.05)[26]. In our study the postoperative period was subdivided into three sub-periods: the early postoperative period (POI), first and second day after surgery, with the intention to better assess the effects of infusion at this stage after surgery. The results of these periods were: POI - Bleeding data, the use of concentrated red blood cells and platelets were not significant, but the hematocrit and hemoglobin had mild elevation,

Cardiac surgery had major limitations in the beginning, in the early twentieth century, for not being able to stop and open the heart to treat intracardiac lesions, but with the development of an artificial heart-lung machine and extracorporeal circulation, the technique has become known and disseminated worldwide as the largest contribution to cardiac surgery and for the world cardiology. However, success was accompanied by problems such as hematological disorders[13], cognitive, and systemic inflammatory reactions[14] and infections[15], resulting from direct blood contact with oxygen and non-endothelial surfaces like metal and plastic. These situations led to the search for solutions to work around the problem. Then emerged coronary revascularization without cardiopulmonary bypass[16], technique followed by other surgeons, with good results in relation to the CPB[14-16]. However, other challenges have emerged, especially in CABG as the difficult access to the lower wall of the heart, great cardiomegalies and severe heart failure, making it difficult to complete revascularization[21]. Another option was the miniaturization of cardiopulmonary bypass described as good alternative by several authors[21-28] and restrictions by other researchers[29-30]. Currently, the mini CPB is establishing itself as a suitable technique to reduce perfusion problems and the use of homologous blood. In our experience, the results for preoperative parameters (Table 1) showed no significant variation,

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but significant (P<0.03). The first and second PO - bleeding was slightly more pronounced in the mini CPB in relation to the CPB (P<0.04), but despite this, hematocrit and hemoglobin remained higher in mini CPB in relation to the CPB (P<0.05). However, it is remarkable that this bleeding did not contribute to the reduction of hematocrit and hemoglobin. These results are similar to those by other authors who also reported high hematocrit[22] and hemoglobin[26], after the use of mini CPB in relation to the CPB. In our research, the comparison between the two perfusion techniques showed better data on mini CPB in relation to the CPB, as referred to CPB and transfusion in the perioperative period and the results of red blood cells and hemoglobin, with statistically significant values​​. The results suggest that the mini CPB was beneficial in reducing the transfusion of packed red blood cells and higher levels of hematocrit and hemoglobin in trans- and postoperative period as mentioned in the literature. More studies are needed on the influences of the type of cardiopulmonary bypass and the use of autotransfusion and we are now working in in this matter to include in another study.

REFERENCES 1. Gibbon Jr. JH, Miller BJ, Feinberg C. An improved mechanical heart and lung apparatus. Med Clin N Am. 1953;1:1603-24. 2. Gibbon JH Jr. Application of a mechanical heart and lung apparatus to cardiac surgery. Minn Med. 1954;37(3):171-85. 3. Lillehei CW, Cohen M, Warden HE, Read RC, Aust JB, DeWall RA, et al. Direct vision intracardiac surgical correction of the tetralogy of Fallot, pentalogy of Fallot, and pulmonary atresia defects: report of first ten cases. Ann Surg. 1955;142(3):418-42. 4. Kirklin JW, Dushane JW, Patrick RT, Donald DE, Hetzel PS, Harshbarger HG, et al. Intracardiac surgery with the aid of a mechanical pump-oxygenator system (Gibbon type): report of eight cases. Proc Staff Meet Mayo Clin. 1955;30(10):201-6. 5. Dewall RA, Gott VL, Lillehei CW, Read RC, Varco RL, Warden HE, et al. A simple, expandable, artificial oxygenator for open heart surgery. Surg Clin North Am. 1956:1025-34. 6. Felipozzi HJ, Santos RG, D’Oliveira LG, Perfeito JS. Cirurgia cardíaca a céu aberto com desvio extracorpóreo da circulação do coração direito. Resultados experimentais e primeiros casos clínicos. Previous note presented on the Department of Surgery at the Paulista Medical Association, on November 16, 1955.

CONCLUSION In our study, the comparison between the two types of perfusion showed better data in the MCPB, from the first period in which the patient was referred to bleeding and transfusion in the perioperative period and the results of red blood cells and hemoglobin, with statistically significant values. The results suggest that the MCPB is beneficial for the reduction of perioperative bleeding, showing higher levels of hematocrit and hemoglobin in trans- and postoperative periods, and especially on reducing the use of concentrated homologous red blood cells, as reported in the literature. We are aware that this matter needs more studies.

7. Zerbini EJ, Jatene AD, Macruz R, Curi N, Verginelli G. Extracorporeal circulation in cardiac surgery. Report of first 50 cases. J Thorac Cardiovasc Surg. 1961;41:205-11. 8. Jasbik W, Meier M, Jasbik A, Pernambuco P, Morais DJ. Modelo aperfeiçoado de coração-pulmão artificial compacto para perfusões com hemodiluição, normoterapia e hipotermia. Arq Bras Cardiol. 1967;20(suppl 1):112. 9. Gomes OM, Conceição DS, Nogueira D Jr, Mengai A, Moraes NL, Tsuzuki S, et al. Normothermal perfusion using am membrane oxigenator. Clinical study. Rev Assoc Med Bras. 1976;22(9):353-5.

Authors’ roles & responsibilities SNP IBZ MSB DP ES RS GPO RS

Analysis and/or interpretation of data; final approval of the manuscript; study design; manuscript writing or critical review of its content Analysis and/or interpretation of data; implementation of projects and/or experiments Analysis and/or interpretation of data; implementation of projects and/or experiments Analysis and/or interpretation of data; implementation of projects and/or experiments Analysis and/or interpretation of data; statistical analysis; study design Analysis and/or interpretation of data; final approval of the manuscript; implementation of projects and/or experiments Analysis and/or interpretation of data; implementation of projects and/or experiments Analysis and/or interpretation of data; final approval of the manuscript; implementation of projects and/or experiments

10. Jatene AD, Souza JE, Paulista PP, de Souza LC, Kormann DS, de Magalhães HM, et al. Direct surgery of coronary artery obstructions. Arq Bras Cardiol 1969;22(6):255-64. 11. Braile DM. Extracorporeal circulation. Rev Bras Cir Cardiovasc. 2010;25(4):III-V. 12. Morais DJ, Jazbik W, Franco S. Perfusão prolongada com hemólise mínima. Uso de plasma em substituição ao sangue no oxigenador. Rev Bras Cir. 1960:42:120. 13. Vohra HA, Whistance R, Modi A, Ohri SK. The inflammatory response to miniaturized extracorporeal circulation: a review of the literature. Mediators Inflamm. 2009;2009:707042.

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14. Ferraris VA, Ferraris SP. Limiting excessive postoperative blood transfusion after cardiac procedures. A review. Tex Heart Inst J. 1995;22(3):216-30.

promising technique for coronary artery bypass grafting. Ann Thorac Surg. 2007;84(5):1515-20. 24. Puehler T, Haneya A, Philipp A, Wiebe K, Keyser A, Rupprecht L, et al. Minimal extracorporeal circulation: an alternative for on-pump and off-pump coronary revascularization. Ann Thorac Surg. 2009;87(3):766-72.

15. Banbury MK, Brizzio ME, Rajeswaran J, Lytle BW, Blackstone EH. Transfusion increases the risk of postoperative infection after cardiovascular surgery. J Am Coll Surg. 2006;202(1):131-8. 16. Kolesov VI, Potashov LV. Surgery of coronary arteries [in Russian]. Eksp Khir Anesteziol. 1965;10(2):3-8.

25. Panday GF, Fischer S, Bauer A, Metz D, Schubel J, El Shouki N, et al. Minimal extracorporeal circulation and off-pump compared to conventional cardiopulmonary bypass in coronary surgery. Interact Cardiovasc Thorac Surg. 2009;9(5):832-6.

17. Benetti FJ, Naselli G, Wood M, Geffner L. Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients. Chest. 1991;100(2):312-6.

26. Perthel M, Klingbeil A, El-Ayoubi L, Gerick M, Laas J. Reduction in blood product usage associated with routine use of mini bypass systems in extracorporeal circulation. Perfusion. 2007;22(1):9-14.

18. Benetti FJ. MINI-off-pump coronary artery bypass graft: longterm results. Future Cardiol. 2010;6(6):791-5.

27. Silva LLM, Andres AJB, Senger R, Stuermer R, Godoi MCM, Correa EFM, et al. Impact of autologous blood transfusion on the use of pack red blood cells in coronary arterial bypass grafting surgery. Rev Bras Cir Cardiovasc. 2013;28(2):183-9.

19. Buffolo E, Andrade JC, Succi JE, Leão LE, Cueva C, Branco JN, et al. Revascularização direta do miocárdio sem circulação extracorpórea. Descrição da técnica e resultados iniciais. Arq Bras Cardiol. 1982;38(5):365-73.

28. Mazzei V, Nasso G, Salamone G, Castorino F, Tomasini A, Anselmi A. Prospective randomized comparison of coronary bypass with minimal extracorporeal circulation system (MECC) versus off-pump coronary surgery. Circulation. 2007;116(16):1761-7.

20. Lima RC, Escobar MAS, Lobo Filho JG, Diniz R, Saraiva A, Césio A, et al. Surgical results of coronary artery bypass grafting without cardiopulmonary bypass: analysis of 3,410 patients. Rev Bras Cir Cardiovasc. 2003;18(3):261-7. 21. Harling L, Punjabi PP, Athanasiou T. Miniaturized extracorporeal circulation vs. off- pump coronary artery bypass grafting: what the evidence shows? Perfusion. 2011;26(Suppl 1):40-7.

29. Ried M, Kobuch R, Rupprecht L, Keyser A, Hilker M, Schmid C, et al. Reduced 30- day mortality in men after elective coronary artery bypass surgery with minimized extracorporeal circulation: a propensity score analysis. BMC Cardiovascular Disord. 2012;12:17.

22. Baikoussis NG, Papakonstantinou NA, Apostolakis E. The “benefits” of the mini- extracorporeal circulation in the minimal invasive cardiac surgery area. J Cardiol. 2014;63(6):391-6.

30. Svitek V, Lonsky V, Mandak J, Krejsek J, Kolackova M, Brzek V, et al. No clear clinical benefit of using mini-invasive extracorporeal circulation in coronary artery bypass grafting in low-risk patients. Perfusion. 2009;24(6):389-95.

23. Immer FF, Ackermann A, Gygax E, Stalder M, Englberger L, Eckstein FS, et al. Minimal extracorporeal circulation is a

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Lima RO, et al. - Relationship between pre-extubation positive end-expiratory ORIGINAL ARTICLE pressure and oxygenation after coronary artery bypass grafting

Relationship between pre-extubation positive endexpiratory pressure and oxygenation after coronary artery bypass grafting Relação entre a pressão expiratória positiva final pré-extubação e a oxigenação após revascularização cirúrgica do miocárdio

Reijane Oliveira Lima1, PT; Daniel Lago Borges1, PT; Marina de Albuquerque Gonçalves Costa1, PT; Thiago Eduardo Pereira Baldez1, PT; Mayara Gabrielle Barbosa e Silva1, PT; Felipe André Silva Sousa1, PT; Milena de Oliveira Soares1, PT; Jivago Gentil Moreira Pinto2, PT

DOI: 10.5935/1678-9741.20150044

RBCCV 44205-1662

Abstract Introduction: After removal of endotracheal tube and artificial ventilation, ventilatory support should be continued, offering oxygen supply to ensure an arterial oxygen saturation close to physiological. Objective: The aim of this study was to investigate the effects of positive-end expiratory pressure before extubation on the oxygenation indices of patients undergoing coronary artery bypass grafting. Methods: A randomized clinical trial with seventy-eight patients undergoing coronary artery bypass grafting divided into three groups and ventilated with different positive-end expiratory pressure levels prior to extubation: Group A, 5 cmH2O (n=32); Group B, 8 cmH2O (n=26); and Group C, 10 cmH2O (n=20). Oxygenation index data were obtained from arterial blood gas samples collected at 1, 3, and 6 h after extubation. Patients with chronic pulmonary disease and those who underwent off-pump, emergency, or combined surgeries were excluded. For statistical analysis, we used Shapiro-Wilk, G, Kruskal-Wallis, and analysis of variance tests and set the level of significance at P<0.05.

Results: Groups were homogenous with regard to demographic, clinical, and surgical variables. There were no statistically significant differences between groups in the first 6 h after extubation with regard to oxygenation indices and oxygen therapy utilization. Conclusion: In this sample of patients undergoing coronary artery bypass grafting, the use of different positive-end expiratory pressure levels before extubation did not affect gas exchange or oxygen therapy utilization in the first 6 h after endotracheal tube removal.

Hospital Universitário da Universidade Federal do Maranhão (HUUFMA), São Luís, MA, Brazil. 2 Universidade Estadual do Piauí (UESPI), Teresina, PI, Brazil.

Correspondence address: Daniel Lago Borges Hospital Universitário da Universidade Federal do Maranhão (HUUFMA) Rua Barão de Itapary, nº 227, Centro - São Luis, MA, Brazil Zip code: 65020-070 E-mail: dlagofisio83@hotmail.com

Descriptors: Oxygenation. Positive-Pressure Respiration, Intrinsic. Coronary Artery Bypass. Resumo Introdução: Após a remoção do tubo endotraqueal e ventilação artificial, o suporte ventilatório deve ser continuado, oferecendo suprimento de oxigênio para garantir uma saturação arterial de oxigênio próxima da fisiológica.

1

This study was carried out at University Hospital of the Federal University of Maranhão (HUUFMA), São Luís, MA, Brazil.

Article received on February 15th, 2015 Article accepted on June 22nd, 2015

Financial support.

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piratória positiva final antes da extubação: Grupo A, 5 cmH2O (n=32); Grupo B, 8 cm H2O (n=26); e grupo C, 10 cmH2O (n=20). Dados do índice de oxigenação foram obtidos a partir de amostras de gases sanguíneos arteriais coletados em 1, 3 e 6 h após a extubação. Pacientes com doença pulmonar crônica e aqueles que foram submetidos à cirurgia sem circulação extracorpórea, de emergência ou combinadas foram excluídos. Para a análise estatística, foram utilizados Shapiro-Wilk, G, Kruskal -Wallis, e análise dos testes de variância e definição do nível de significância em P<0,05. Resultados: Os grupos foram homogêneos em relação às variáveis ​​demográficas, clínicas e cirúrgicas. Não houve diferenças estatisticamente significativas entre os grupos nas primeiras 6 h após extubação no que diz respeito aos índices de oxigenação e a utilização de oxigenoterapia. Conclusão: Nesta amostra de pacientes submetidos à revascularização do miocárdio, o uso de diferentes níveis de pressão expiratória positiva final antes da extubação não afetou as trocas gasosas ou utilização de oxigenoterapia nas primeiras 6h após a remoção do tubo endotraqueal.

Abbreviations, acronyms & symbols BMI CABG FiO2 FiO2N ICU IMV NIV PaO2 PaO2I PEEP PSV SaO2 SBT

Body mass index Coronary artery bypass grafting Inspired oxygen fraction Necessary inspired oxygen fraction Intensive Care Unit Invasive mechanical ventilation Noninvasive ventilation Arterial oxygen partial pressure Ideal arterial oxygen partial pressure Positive end-expiratory pressure Pressure support ventilation Arterial oxygen saturation Spontaneous breathing trial

Objetivo: O objetivo deste estudo foi investigar os efeitos da pressão expiratória positiva final antes de extubação nos índices de oxigenação de pacientes submetidos à cirurgia de revascularização miocárdica. Métodos: Ensaio clínico randomizado com 78 pacientes submetidos à cirurgia de revascularização do miocárdio, divididos em três grupos e ventilados com diferentes níveis de pressão ex-

Descritores: Oxigenação. Respiração por Pressão Positiva Intrínseca. Ponte de Artéria Coronária.

INTRODUCTION

pressure support ventilation (PSV) to determine whether a patient would tolerate IMV interruption. This ventilation mode consists of a pressure support of 7 cm H2O (the minimum level to overcome circuit resistance), positive end-expiratory pressure (PEEP) of 5-8 cm H2O (nearest to physiological values), and inspired oxygen fraction (FiO2) < 40%. This trial lasts 30-120 min and is helpful in identifying patients who are able to maintain spontaneous breathing[8]. Following endotracheal tube and artificial ventilation removal, respiratory support should be provided with oxygen to ensure arterial oxygen saturation (SaO2) close to physiological levels (95%). Oxygen therapy can be offered using a nasal catheter, nebulization mask, or Venturi system[6]. In this study, we investigated the effects of different PEEP levels applied during SBT on oxygenation indices in patients undergoing CABG.

Coronary artery bypass grafting (CABG) is a therapeutic modality widely used to treat coronary artery disease, minimize symptoms, improve cardiac function, and improve survival[1,2]. Intraoperative conditions, such as general anesthesia, manual compression of the left lower lung lobe during exposure of the posterior heart surface, manual compression of the right lung during cannulation of the inferior vena cava, manual compression of lungs during dissection of the internal mammary artery and apnea during cardiopulmonary bypass (CPB) may impair pulmonary function[3]. Thus, pulmonary complications occur in up to 60% patients undergoing CABG[4]. Invasive mechanical ventilation (IMV) is essential during the first few hours after CABG to allow recovery from anesthesia and reestablish homeostasis[5]. Typical restoration of hemodynamic stability occurs 5–6 h after surgery in uncomplicated CABG. This interval also correlates with regaining of consciousness and IMV weaning[6]. When IMV is no longer required, the most appropriate method for its discontinuation must be determined[7]. The spontaneous breathing trial (SBT) is a simple method using

METHODS We performed a randomized clinical trial with 78 patients undergoing CABG between August 2013 and March 2014 who were admitted to the Cardiovascular Intensive Care Unit (ICU) at Hospital Universitário da Universidade Federal do Maranhão, in São Luís, Maranhão, Brazil. We

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excluded patients with chronic obstructive pulmonary disease and those undergoing emergency, off-pump, or combined surgeries. We excluded patients who required surgical reintervention or noninvasive ventilation during the first 6 h after extubation. Before surgery, patients received explanations and information about the research. After surgery, data were collected from physiotherapy evaluation forms and medical records. All data were registered in a form that captured preoperative, intraoperative, and postoperative periods. All included patients underwent general anesthesia and median sternotomy. After ICU admission, mechanical ventilation was applied using an Evita 2 Dura (Dräger Medical, Lübeck, Germany). Patients were ventilated in volume-controlled mode, according to the routine protocol, with the following settings: a tidal volume of 6–8 mL/kg, respiratory rate of 14 bpm, inspiratory flow of 8-10 times the minute volume, inspiratory time of 1 s, and inspired oxygen fraction of 40%. During the preoperative period, patients were randomized into groups by simple draw, and this information was shared with the ICU care providers. SBT was initiated once the following clinical conditions were met: hemodynamic stability, absence of bleeding or minimal bleeding, absence of vasopressor use or low and stable doses of vasopressors, Glasgow Coma Scale ≥ 10 and strong respiratory drive. The spontaneous breathing trial was administered using pressure support ventilation (support pressure 7 cm H2O and FiO2 30%). The sample was divided into three groups: Group A, PEEP = 5 cm H2O; Group B, PEEP = 8 cm H2O; and Group C, PEEP = 10 cm H2O. Extubation was performed after 30–120 min with no destabilization signs. Following extubation, all patients received additional oxygen support by Venturi mask (Galemed Corporation, Wu-Jia, Taiwan) with an FiO2 of 31% to ensure arterial oxygen saturation close to physiological levels (around 95%). Arterial blood samples were collected before extubation and at 1, 3, and 6 h after mechanical ventilation withdrawal. Samples were processed by an ABL 800 FLEX blood gas analyzer (Radiometer, Bronshoj, Denmark), according to the routine protocol. We then identified the arterial oxygen partial pressure (PaO2) and PaO2/FiO2 ratio. Following the first arterial blood gas analysis after extubation, oxygen support was adjusted according to the necessary inspired oxygen fraction (FiO2N). To estimate the ideal arterial oxygen partial pressure (PaO2I) for each patient, we used the following equation to account for age and supine position: PaO2I = 109 − (0.43 × age)[9]. The inspired oxygen fraction provided following extubation was calculated according to the following formula: FiO2N = FiO2K × PaO2I/PaO2K, in which FiO2N = the inspired oxygen fraction necessary after extubation, FiO2K = the inspired oxygen fraction applied at the moment of arterial blood sample collection, PaO2I = the ideal arterial oxygen partial pressure, and PaO2K = the arterial oxygen partial pressure as measured

by the last arterial blood gas. Oxygen was administered by Venturi mask using the following criteria: FiO2N <21%: room air; FiO 2N = 21%–24%: blue connector, FiO2 24%, O2 flow 4 lpm; FiO2N = 24.1%–28%: yellow connector, FiO2 28%, O2 flow 4 lpm; FiO2N = 28.1%–31%: white connector, FiO2 31%, O2 flow 4 lpm; FiO2N 31.1%–35%: green connector, FiO2 35%, O2 flow 6 lpm; FiO2N 35.1%–40%: red connector, FiO2 40%, O2 flow 8 lpm; FiO 2N >40%: orange connector, FiO2 50%, O2 flow 12 lpm. When noninvasive ventilation (NIV) was required following extubation, it was applied, as per the routine protocol, according to the individual’s needs. It is noteworthy that patients who used NIV during the first 6 h after extubation were excluded. Ethical approval was obtained from the local Ethics Committee (protocol No. 327.798), as required by Resolution 466/12 of the National Health Council. All patients provided written informed consent. Data were evaluated using the Stata/SE statistical software version 11.1 (StataCorp, College Station, TX, USA). To test normality, we used the Shapiro–Wilk test. Quantitative variables were described as means and standard deviations, and differences were determined using the Student’s t, ANOVA, or Kruskal–Wallis test, depending on normality. Qualitative variables were expressed as proportions and tested by G-test and William’s correction. Results were considered statistically significant when P value was <0.05. RESULTS Ninety patients were randomized and underwent CABG during the study period. Of these, twelve (four of each group) were excluded because of postoperative surgical reintervention (6) and noninvasive ventilation use during the first 6 h after extubation (6) (Figure 1). Therefore, the final sample included 78 patients, who were predominantly male (69.3%) and from the countryside (53.8%), with a mean age of 61.7±8.6 years and body mass index of 26.1±3.7 kg/m2. Groups did not differ significantly with regard to demographic, clinical, or surgical variables, as seen in Tables 1 and 2. The mean mechanical ventilation duration was 12.8±6.9 h. Patients in Group A (PEEP 5 cm H2O) were ventilated for 13.6±8.1 h, whereas those in Group B (PEEP 8 cm H2O) were ventilated for 11.7±6 h and those in Group C (PEEP 10 cm H2O) were ventilated for 13.2±4.8 h (P=0.69). There were no differences in mean gas exchange values (PaO2/FiO2) between groups at 1, 3, and 6 h after extubation (Table 3).

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Fig. 1 - Consort flow diagram.

Table 1. Demographic and clinical data for patients undergoing CABG. Variables Gender Male Female Age (years) Origin Capital Countryside BMI (kg/m2) Comorbidities Hypertension Diabetes mellitus Dyslipidemia Smoking Myocardial infarction

Group A (n=32)

Group B (n=26)

Group C (n=20)

TOTAL (%)

26 6 61.3±9.4

16 10 60.3±6.7

12 8 64.2±10

54 (69.3) 24 (30.7) 61.7±8.6

20 12 25.6±3.7

12 14 27.4±4.5

4 16 25.3±2.4

36 (46.2) 42 (53.8) 26.1±3.7

20 12 8 6 6

18 12 12 10 2

12 6 4 6 2

50 (64.1) 30 (38.4) 24 (30.7) 22 (28.2) 10 (12.8)

P 0.49a 0.64b 0.15a 0.55b 0.81a 0.52a 0.40a 0.49a 0.69a

BMI=body mass index. aG test. bKruskal-Wallis test

Table 2. Surgical data for patients undergoing CABG. Variables Number of bypasses Number of drainage tubes Pump time (min) Aortic clamp time (min) Surgery time (min)

Group A (n = 32) 3 (2.75;3) 2 (2;2) 83.4 ± 21.7 60.9 ± 19.2 220.9 ± 25.3

Group B (n = 26) 2 (2;3) 2 (2;2) 67.3 ± 25.3 48.4 ± 20.2 230.5 ± 62.1

Group C (n = 20) 3 (2;3) 2 (2;2) 89.4 ± 23.5 61.5 ± 17 257.6 ± 64.9

P 0.22a 0.56a 0.08b 0.15b 0.22a

Data shown as the mean±standard deviation or median (1st quartile; 3rd quartile). aANOVA. bKruskal-Wallis test

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Table 3. Comparison of gas exchange mean (mmHg) between the three groups of patients undergoing CABG.

mechanically ventilated at 5, 8, or 10 cm H2O of PEEP, Borges et al.[16] showed that the highest PEEP levels may increase respiratory mechanics and provide better oxygenation indices in the immediate postoperative period. Our hypothesis that application of higher PEEP levels throughout SBT would improve oxygenation after extubation was not supported by our measurements during the first 6 h after extubation. The results were consistent with those measured in the randomized clinical trial by Marvel et al.[17], in which patients undergoing CABG and ventilation with PEEP of 0, 5, or 10 cm H2O did not experience a sustained arterial oxygenation benefit from higher PEEP levels. A question that arose during our research was what PEEP level would be considered physiological to avoid alveolar collapse while performing SBT, given that the “expiratory delay function” of the glottis (which serves as an organic PEEP mechanism to prevent or minimize alveolar collapse) is removed during artificial ventilation[18]? During mechanical ventilation of adult patients, PEEP is generally set to 3–5 cm H2O, as this is considered physiological[19]. However, our study provided some evidence that levels between 5 and 8 cm H2O, possibly up to 10 cm H2O, may more closely mimic normal respiratory physiology for such patients. The knowledge of physical therapy was found to be generally applied across the entire treatment process[20]. Physical therapists play an important role in conducting patient-screening protocols for mechanical ventilation weaning[21,22]. Our research emphasizes identification of optimal variables during weaning as fundamental to this process so as to minimize patient complications.

Groups/times Group A Group B Group C P

1st hour 320.5±65 326.9±84.1 308.3±49.9 0.92

3rd hour 347.7±75.9 332.5±97.3 313.3±56.9 0.64

6th hour 333.1±67.9 343.5±118.5 311.5±80.3 0.77

Data shown as the mean±standard deviation. Kruskal-Wallis test.

Table 4. Comparison of arterial oxygen saturation (%) between the three groups of patients undergoing CABG. Groups/times Group A Group lB Group C P

1st hour 97.6±0.9 97.2±1.9 97.5±1.2 0.84

3rd hour 97.0±0.9 96.8±1.9 96.7±1.4 0.86

6th hour 96.8±0.8 96.9±1.2 96.8±1.1 0.65

Data shown as the mean±standard deviation. Kruskal-Wallis test.

Table 5. Comparison of inspired oxygen fraction (%) applied after extubation between the three groups of patients undergoing CABG. Groups/times Group A Group B Group C P

1st hour 26±5 27±5 27±5 0.61

3rd hour 27±6 28±7 27±6 0.70

6th hour 27±5 28±8 27±7 0.77

Data shown as the mean ± standard deviation. Kruskal-Wallis test

CONCLUSION

Mean arterial oxygen saturation and inspired oxygen fraction did not differ between groups at 1, 3, and 6 h after extubation (Tables 4 and 5).

In this sample of patients undergoing CABG, the use of different PEEP levels before extubation did not affect gas exchange or oxygen therapy utilization in the first 6 h after endotracheal tube removal.

DISCUSSION Gas exchange impairment is a significant complication during the CABG postoperative period[10]. In thoracic surgeries, these changes may be related to intraoperative procedures, such as mechanical ventilation with low volumes and PEEP, pain, and thoracotomy (which alters chest wall compliance)[11,12]. Therefore, we chose to evaluate oxygenation indices after extubation, because they properly reflect changes in pulmonary function following on-pump surgery[13]. To reopen collapsed lung units and improve arterial oxygenation following thoracic surgery, different PEEP levels have been proposed[14]. Dongelmans et al.[15], who compared high versus physiological PEEP (10 vs. 5 cm H2O) after CABG, showed that the highest PEEP levels improve oxygenation and lung compliance but are associated with increased mechanical ventilation duration. In their randomized clinical trial of 136 patients undergoing CABG who were

Authors’ roles & responsibilities ROL DLB

MAGC TEPB MGBS FASS MOS JGMP

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Analysis and/or interpretation of data; study design; implementation of projects and/or experiments; manuscript writing or critical review of its content Analysis and/or interpretation of data; statistical analysis; final approval of the manuscript; study design; implementation of projects and/or experiments; manuscript writing or critical review of its content Conduct of operations and/or experiments Conduct of operations and/or experiments Conduct of operations and/or experiments Conduct of operations and/or experiments Conduct of operations and/or experiments Analysis and/or interpretation of data; manuscript writing or critical review of its content

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13. Cui H, Zhang M, Xiao F, Li Y, Wang J, Chen H. Comparison and correlative analysis of pulmonary function markers after extracorporeal circulation. Beijing Da Xue Xue Bao. 2013;35(2):195-9.

2. Rocha LA, Maia TF, Silva LF. Diagnóstico de enfermagem em pacientes submetidos à cirurgia cardíaca. Rev Bras Enferm. 2006:59(3);321-6.

14. Dyhr T, Nygård E, Laursen N, Larsson A. Both lung recruitment maneuver and PEEP are needed to increase oxygenation and lung volume after cardiac surgery. Acta Anaesthesiol Scand. 2004;48(2):187-97.

3. Zocrato LBR, Machado MGR. Fisioterapia respiratória no pré e pós-operatório de cirurgia cardíaca. In: Machado MGR. Bases da fisioterapia respiratória: terapia intensiva e reabilitação. Rio de Janeiro: Guanabara Koogan; 2008. p.338-62.

15. Dongelmans DA, Hemmes SN, Kudoga AC, Veelo DP, Binnekade JM, Schultz MJ. Positive end-expiratory pressure following coronary artery bypass grafting. Minerva Anestesiol. 2012;78(7):790-800.

4. Nardi C, Otranto CPM, Piaia IM, Forti EMP, Fantini B. Avaliação da força muscular, capacidades pulmonares e função pulmonar respiratória de pacientes submetidos à cirurgia cardíaca. In: 4ª Mostra Acadêmica e Congresso de Pesquisa da UNIMEP [on line]: 2006. Out, 24-26. Piracicaba. Anais eletrônicos [Cited 2015 Jul 23]. Available from: http//www.unimep.br/phpg/ mostraacademica/anais/4mostra/pdfs/171pdf

16. Borges DL, Nina VJS, Costa MAG, Baldez TEP, Santos NP, Lima IM, et al. Effects of different PEEP levels on respiratory mechanics and oxygenation after coronary artery bypass grafting. Rev Bras Cir Cardiovasc. 2013;28(3):380-5.

5. Lourenço IS, Franco AM, Bassetto S, Rodrigues AJ. Pressure support-ventilation versus spontaneous breathing with “T-Tube” for interrupting the ventilation after cardiac operations. Rev Bras Cir Cardiovasc. 2013;28(4):455-61.

17. Marvel SL, Elliott CG, Tocino I, Greenway LW, Metcalf SM, Chapman RH. Positive end-expiratory pressure following coronary artery bypass grafting. Chest. 1986;90(4):537-41.

6. Umeda IIK. Manual de fisioterapia na cirurgia cardíaca: guia prático. Barueri: Manole; 2004.

18. Annest SJ, Gottlieb M, Paloski WH, Stratton H, Newell JC, Dutton R, et al. Detrimental effects of removing endexpiratory pressure prior to endotracheal extubation. Ann Surg. 1980;191(5):539-45.

7. Piotto RF, Maia LN, Machado MN, Orrico SP. Effects of the use of mechanical ventilation weaning protocol in the Coronary Care Unit: randomized study. Rev Bras Cir Cardiovasc. 2011;26(2):213-21.

19. David CM. Ventilação Mecânica: Da fisiologia à prática clínica. 2ª ed. Rio de Janeiro: Revinter; 2011.

8. Goldwasser R, Farias A, Freitas EE, Saddy F, Amado V, Okamoto V. III Consenso Brasileiro de Ventilação Mecânica. Desmame e interrupção da ventilação mecânica. J Bras Pneum. 2007;33 (Suppl 2S):S128-S136.

20. Ryu YU, Park J. Medical and narrative use of physical therapy knowledge in clinical reasoning by Korean physical therapists. J Phys Ther Sci. 2011;23(2):251-4.

9. Diniz GCLM, Machado MGR. Oxigenoterapia. In: Machado MGR. Bases da fisioterapia respiratória: terapia intensiva e reabilitação. Rio de Janeiro: Guanabara Koogan; 2008. p.182-97.

21. Ely EW, Meade MO, Haponik EF, Kollef MH, Cook DJ, Guyatt GH, et al. Mechanical ventilator weaning protocols driven by nonphysician health-care professionals: evidence-based clinical practice guidelines. Chest. 2001;120(6 Suppl):454S-63S.

10. Singh NP, Vargas FS, Cukier A, Terra-Filho M, Teixeira LR, Light RW. Arterial blood gases after coronary artery bypass surgery. Chest. 1992:102(5);1337-41.

22. Plani N, Becker P, van Aswegen H. The use of a weaning and extubation protocol to facilitate effective weaning and extubation from mechanical ventilation in patients suffering from traumatic injuries: a non-randomized experimental trial comparing a prospective to retrospective cohort. Physiother Theory Pract. 2013;29(3):211-21.

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Silva PS, et al. - EvaluationARTICLE of the influence of pulmonary hypertension in ORIGINAL ultra-fast-track anesthesia technique in adult patients undergoing cardiac surgery

Evaluation of the influence of pulmonary hypertension in ultra-fast-track anesthesia technique in adult patients undergoing cardiac surgery Avaliação da influência da hipertensão pulmonar na técnica anestésica ultra-fast-track em pacientes adultos submetidos à cirurgia cardíaca

Paulo Sérgio da Silva1, MD, TEA-SBA; Márcio Portugal Trindade Cartacho2, MD, TEA-SBA; Casimiro Cardoso de Castro3, MD; Marcello Fonseca Salgado Filho4, MD, TEA-SBA, MSc; Antônio Carlos Aguiar Brandão5, MD, TSA-SBA; PhD

DOI: 10.5935/1678-9741.20150042

RBCCV 44205-1663

Abstract Objective: To evaluate the influence of pulmonary hypertension in the ultra-fast-track anesthesia technique in adult cardiac surgery. Methods: A retrospective study. They were included 40 patients divided into two groups: GI (without pulmonary hypertension) and GII (with pulmonary hypertension). Based on data obtained by transthoracic echocardiography. We considered as the absence of pulmonary hypertension: a pulmonary artery systolic pressure (sPAP) <36 mmHg, with tricuspid regurgitation velocity <2.8 m/s and no additional echocardiographic signs of PH, and PH as presence: a sPAP >40 mmHg associated with additional echocardiographic signs of PH. It was established as influence of pulmonary hypertension: the impossibility of extubation in the operating room, the increase in the time interval

for extubation and reintubation the first 24 hours postoperatively. Univariate and multivariate analyzes were performed when necessary. Considered significant a P value <0.05. Results: The GI was composed of 21 patients and GII for 19. All patients (100%) were extubated in the operating room in a medium time interval of 17.58±8.06 min with a median of 18 min in GII and 17 min in GI. PH did not increase the time interval for extubation (P=0.397). It required reintubation of 2 patients in GII (5% of the total), without statistically significant as compared to GI (P=0.488). Conclusion: In this study, pulmonary hypertension did not influence on ultra-fast-track anesthesia in adult cardiac surgery.

Hospital Regional Alto Vale (HRAV), Rio do Sul, SC, Brazil. Hospital Regional Terezinha Gaio Basso and Hospital São Miguel, São Miguel do Oeste, SC, Brazil. 3 Hospital dos Cajueiros de Luanda, Luanda, Angola. 4 Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, MG, Brazil. 5 Universidade do Vale do Sapucaí (UNIVAS), Pouso Alegre, MG, Brazil.

Correspondence address: Paulo Sérgio da Silva Hospital Regional Alto Vale (HRAV) Rua Tuiutí, 218, Centro - Rio do Sul, SC, Brazil Zip code: 89160-922 E-mail: psminas@ig.com.br

Descriptors: Anesthesia. Airway Extubation. Hypertension, Pulmonary. Heart Valve Diseases. Cardiovascular Surgical Procedures.

1 2

This study was carried out at Josina Machel Hospital, Luanda, Angola.

Article received on January 12th, 2014 Article accepted on June 21st, 2015

No financial support.

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ecocardiograma transtorácico, considerou-se como ausência de hipertensão pulmonar: uma pressão sistólica da artéria pulmonar 36 mmHg, com velocidade de regurgitação tricúspide <2,8 m/s e ausência de sinais ecocardiográficos adicionais de hipertensão pulmonar; e como presença de hipertensão pulmonar: uma PSAP >40 mmHg associada a sinais ecocardiográficos adicionais de hipertensão pulmonar. Foi estabelecida como influência da HP: a impossibilidade de extubação na sala cirúrgica, o aumento no intervalo de tempo para extubação e a necessidade de reintubação nas primeiras 24h de pós-operatório. Foram realizadas análises univariada e multivariada quando necessário. Foi considerado como significativo um valor de P<0,05. Resultados: O GI foi composto por 21 pacientes e o GII por 19. Todos os pacientes (100%) foram extubados na sala cirúrgica em um intervalo de tempo médio de 17,58±8,06 min, com uma mediana de 18 min no GI e 17 min no GII. A hipertensão pulmonar não aumentou o intervalo de tempo para extubação (P=0,397). Foi necessária a reintubação de 2 pacientes do GII (5% do total), estatisticamente sem significância em relação ao GI (P=0,488). Não houve óbitos durante a internação dos pacientes. Conclusão: Neste estudo a hipertensão pulmonar não teve influência na técnica anestésica ultra-fast-track em cirurgia cardíaca de adultos.

Abbreviations, acronyms & symbols Ao Aortic CABG Coronary artery bypass graft CPB Cardiopulmonary bypass CVP Central venous pressure DM Diabetes mellitus ECG Electrocardiogram IAC Interatrial communication ICU Intensive Care Unit LVEF Left ventricular ejection fraction PAVSD Partial atrioventricular septal defect PFO Patent foramen ovale PH Pulmonary hypertension PO Postoperative PVR Pulmonary vascular resistance RV Right ventricle SAH Systemic arterial hypertension sPAP Systolic pulmonary artery pressure TEA Thoracic epidural analgesia UFT Ultra-fast-track UFTA Ultra-fast-track anesthesia

Resumo Objetivo: Avaliar a influência da hipertensão pulmonar na técnica anestésica ultra-fast-track em cirurgia cardíaca de adultos. Métodos: Estudo retrospectivo. Foram incluídos 40 pacientes divididos em dois grupos: GI (sem hipertensão pulmonar) e GII (com hipertensão pulmonar). Com base em dados obtidos por

Descritores: Anestesia. Extubação. Hipertensão Pulmonar. Doenças das Valvas Cardíacas. Procedimentos Cirúrgicos Cardiovasculares.

INTRODUCTION

the operating room (ultra-fast-track anesthesia – UFTA)[2]. Several studies have shown the safety of this new type of anesthetic management in adult and pediatric patients[7-11]. Pulmonary hypertension (PH) is common in patients with heart disease, being the echocardiography the most useful noninvasive test for evaluating patients with clinical features of PH[12]. The literature does not indicate whether PH, as a prior disease, affects the UFTA of adult patients undergoing cardiac surgery. Most available studies have been performed in children or limited to reports of a few cases in adults with conflicting results. The aim of this study was to assess the influence of the previous PH in UFTA of adult patients undergoing cardiac surgery.

The anesthetic management of patients undergoing cardiac surgery had as standard anesthetic technique the use of high doses of opioids. With this technique patients were extubated after long hours postoperatively, which caused a longer stay in the intensive care unit (ICU), possible complications and increased morbidity and mortality, generating higher costs to the system health[1]. From the 90s, several studies have shown that the use of anesthetic technique that enabled early extubation after cardiac surgery, is a key factor for early discharge[1,2]. Krohn et al.[3], described the first rapid management which has been named fast-track. Anesthetic practice adapted to fast-track uses shortterm drug or the long-term low dose, targeting an extubation within 6 to 8 hours (fast-track anesthesia)[1,2]. Other studies have shown that early extubation is safe and is associated with lower costs[4,5]. This type of management is considered the current standard in various referral centers for cardiac surgery[2]. Walji et al.[6] described a protocol that allowed ultra-early hospital discharge, between the 1st and the 4th postoperative (PO) day, which became known as ultra-fast-track management (UFT). This term was extended later to anesthesia as a reference to an anesthetic technique that allows ultra-early extubation in

METHODS This was a retrospective study in which the medical records of patients undergoing cardiac surgery and UFTA were analyzed in the period from January to June 2011, at the Cardiovascular Surgery Service of the Josina Machel Hospital - Luanda/Angola. Forty patients were included in the study. Patients were divided into two groups: Group 1 (GI) - without PH; Group 2 (GII) - with PH.

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Data for determining the presence or absence of PH were obtained by transthoracic echocardiography. It was considered as the absence of PH: a systolic pulmonary artery pressure (sPAP) <36 mmHg, with tricuspid regurgitant velocity <2.8 m/s and no additional echocardiographic signs of PH[13,14]. The presence of PH was considered when: sPAP >40 mmHg associated with additional echocardiographic signs of PH[13,14]. The following patients were excluded from the study: patients with sPAP between 36 and 40 mmHg (patients who would need further investigation to confirm PH)[14], patients under the age of 18 years, who underwent surgery without CPB, with aortic disease or undergoing aortic surgery. The anesthetic technique used was balanced: intravenous and inhalation. The monitoring was performed with pulse oximetry, cardioscopy (ECG), invasive blood pressure measurement, measurement of central venous pressure (CVP), capnography, measurement of nasopharyngeal temperature and measure of urine volume per urinary catheterization. Serial measurement of arterial blood gases, electrolytes dosage and erythrocyte were performed. The induction of anesthesia was performed with etomidate (0.3 mg/kg), lidocaine (1 mg/kg), fentanyl (2 - 5 µg/kg), remifentanil (0.3 µg/kg/ min) and rocuronium (1 mg/kg). Maintenance was performed with isoflurane (1.2%) and remifentanil (0.1 - 0.3 µg/kg/min). Postoperative analgesia was performed with spinal morphine (300 μg) (in patients without contraindications) and dipyrone (30 mg/kg/dose) intravenously. In patients not receiving spinal anesthesia, intravenous doses of dipyrone (30 mg/kg/dose), ketorolac (1 mg/kg) and tramadol (1 mg/kg) were administered. Reversal of neuromuscular blockade was performed in all patients. We considered as criteria for extubation patients who presented at the end of surgery: 1) hemodynamically stable or under use of low dose vasoactive drug; 2) balanced at the electrolyte and acid-base viewpoint (by arterial blood gases); 3) with adequate analgesia; 4) with enough level of consciousness to

the respiratory control; 5) without respiratory complications from the surgical procedure; 6) without major bleeding. Three factors were assessed to determine if there was PH’s influence on UFTA, leading to failure in technique: 1) the impossibility of extubation in the operating room; 2) the extended period of time to extubation; 3) the need for reintubation within 24 hours PO. Statistical analysis was performed using R software version 3.0.3. To verify the homogeneity of the groups regarding the study variables, the Mann-Whitney test for quantitative variables and the chi-square test and Fisher exact for categorical variables were used. To assess whether there were factors that influence the time interval for extubation we used Log-Linear regression analysis via Quasi-Likelihood, with univariate and multivariate analyzes through the Backward and Forward procedures, and the final regression being for the time extubation called Log-Linear Stepwise. To assess whether there were factors that influence the reintubation the univariate analysis was performed, using for such, Mann-Whitney tests for quantitative variables and the Fisher exact test for categorical variables. At the end of all the analyzes the Statistical significance was defined with “P” values less than 5% (P<0.05). This study was approved by the Research Ethics Committee of the Josina Machel Hospital where the written informed consent of the patients was delivered. RESULTS The 40 patients studied had undergone various types of surgery, the vast majority valve surgeries, predominantly surgeries involving the mitral valve. The number of patients distributed between the two groups was very close, and the GI was composed of 21 patients and GII composed of 19 patients. In GII most patients (63.16%) had moderate PH, and the average sPAP in this group was 64.15±17.78 mmHg (minimum sPAP of 44 mmHg and maximum of 121 mmHg) (Tables 1 and 2).

Table 1. Types of surgeries performed. N Mitral valve replacement Mitral valve replacement + tricuspid plasty Mitral valve replacement + PFO Correction Mitral valve replacement + IAC Correction Aortic valve replacement (AoVR) Mitral valve replacement + AoVR Tricuspid valve replacement IAC Correction Resection of subaortic membrane Correction of pulmonary stenosis Correction of PAVSD Total

19 4 1 1 6 2 1 3 1 1 1 40

GI (without PH) 10 1 1 1 6 1 0 0 1 0 0 21

GII (with PH) 9 3 0 0 0 1 1 3 0 1 1 19

PH=pulmonary hypertension; PFO=patent foramen ovale; IAC=interatrial communication; PAVSD=partial atrioventricular septal defect

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Silva PS, et al. - Evaluation of the influence of pulmonary hypertension in ultra-fast-track anesthesia technique in adult patients undergoing cardiac surgery

Table 2. sPAP in GII patients. sPAP (mmHg) Slight PH Moderate PH Severe PH

Medium 64.15

36 - 50 51 - 70 >70

N 3 12 4

SD 17.78

Min. 44

% 15.79% 63.16% 21.05%

Max. 121

sPAP=systolic pulmonary artery pressure; SD=standard deviation; Min.=minimum; Max.=maximum; PH=pulmonary hypertension

Table 3. Characteristics of patients and perioperative - Frequency for categorical variables. Variables Group

GI (without PH) GII (with PH)

N 21 19

% 52.5% 47.5%

Gender

Female Male

25 15

62.5% 37.5%

EuroSCORE

Low Medium High

28 11 1

70.0% 27.5% 2.5%

DM

No Yes

40 0

100.0% 0.0%

SAH

No Yes

31 9

77.5% 22.5%

COPD

No Yes

40 0

100.0% 0.0%

Smoking

No Yes

36 4

90.0% 10.0%

Spinal analgesia

No Yes

32 8

80.0% 20.0%

Dobutamine

No Yes

32 8

80.0% 20.0%

Sodium nitroprusside

No Yes

9 31

22.5% 77.5%

Extubation in the operating room

No Yes

0 40

0.0% 100%

Reintubation

No Yes

38 2

95.0% 5.0%

Deaths during hospitalization

No Yes

40 0

100% 0.0%

PH=pulmonary hypertension; DM=diabetes mellitus; SAH=systemic arterial hypertension; COPD=chronic obstructive pulmonary disease

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Most patients were female, representing 52% of GI patients and 74% of GII. The EuroSCORE was of low risk in 86% of GI patients and 53% of GII. The average age of patients was 34.9±14.23 years (median 33 years in GI and 36 years in GII), the average weight of 53.40±12.53 kg (median 52 kg in GI and 47 kg in GII) and the average height of 1.62±0.10 meters (median of 1.7 meters in GI and 1.6 meters

in GII). No patient had diabetes mellitus (DM) or chronic obstructive pulmonary disease (COPD). Most were not carriers of systemic arterial hypertension (SAH) (77.5%) or had the smoking habit (90%). Left ventricular ejection fraction (LVEF) average was 62±9% (median 60% in both groups). The spinal analgesia was performed in 8 patients (20%). The mean duration of surgery was 156.23±40.97 minutes (median

Table 4. Characteristics of patients and perioperative - Descriptive measures of quantitative variables. Variables Medium Age (years) 34.90 Weight (kg) 53.40 Height (m) 1.62 LVEF (%) 62.00 Surgery Time (min) 156.23 CPB Time (min) 56.75 Aortic clamping time (min) 41.93 ∆T extubation 17.58

SD 14.23 12.53 0.10 9.00 40.97 25.32 19.22 8.06

Min. 18.00 35.00 1.35 41.00 80.00 29.00 17.00 5.00

Q1 21.00 45.00 1.55 57.00 122.00 40.50 29.50 11.00

Q2 33.00 50.00 1.63 64.00 152.50 49.50 36.50 17.50

Q3 43.00 59.75 1.69 68.00 178.00 64.00 45.50 21.50

Máx. 71.00 94.00 1.90 75.00 275.00 160.00 115.00 47.00

Q1=1st quartile; Q2=2nd quartile (median); Q3=3rd quartile; Kg=kilograms; m=meters; min=minutes; LVEF=left ventricular ejection fraction in %; CPB=cardiopulmonary bypass; ∆T extubation=time interval for extubation (time between turning off the halogenated gas and patient's extubation)

Table 5. Characteristics of patients - Homogeneity of groups. Variables

Gender

Female Male

Age (years) Weight (kg) Height (m)

GI (without PH) 11 52% 10 48%

Groups

GII (with PH) 14 74% 5 26%

33.0 52.0 1.7

[22.0; 41.0] [46.5; 66.0] [1.6; 1.7]

36.0 47.0 1.6

[21.0; 47.0] [43.2 ; 52.5] [1.5; 1.7]

P-value

0.165 0.654 0.036 0.026

DM

Yes No

0 21

0% 100%

0 19

0% 100%

SAH

Yes No

4 17

19% 81%

5 14

26% 74%

COPD

Yes No

0 21

0% 100%

0 19

0% 100%

Smoking

Yes No

2 19

10% 90%

2 17

11% 89%

1.000

60

[50; 70]

60

[60; 70]

0.849

18 3 0

86% 14% 0%

10 8 1

53% 42% 5%

0.051

LVEF (%) EuroSCORE

Low Medium High

0.712

For categorical variables were presented absolute and relative frequency and for quantitative variables was presented Q2 [Q1;Q3]. PH=pulmonary hypertension; DM=diabetes mellitus; SAH=systemic arterial hypertension; COPD=chronic obstructive pulmonary disease; LVEF=left ventricular ejection fraction

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158 minutes in GI and 150 minutes in GII), the cardiopulmonary bypass (CPB) 56.75±25.32 minutes (median 48 minutes in GI and 51 minutes in GII) and the aortic clamping 41.93±19.22 minutes (median 35 minutes in GI and 38 minutes in GII). Dobutamine has been used on 8 patients (20%) and sodium nitroprusside in 31 patients (77.5%). All patients (100%) were extubated in the operating room and the average time interval for extubation was 17.58±8.06 minutes (median 18 minutes in GI and 17 minutes in GII). It required reintubation of two patients (5%) in the first 24 hours PO. There were no deaths during hospitalization of patients (Tables 3 to 6). The groups were not homogeneous with respect to two variables, the weight and height, and the median for these variables were significantly higher in GI when compared to

GII, with a P value of 0.036 for weight and 0.026 for height (Table 5). Since they were not homogeneous groups, to assess the possible variables which influence the time interval for extubation, it was necessary to perform univariate and multivariate analyzes. From the univariate analysis the only factor that could have influenced the time interval for extubation was the height. When performing multivariate analysis, controlled by the factor group (GII), which is the aim of the study, it was observed that the height influences the time interval for extubation in inverse ratio, so that the lower the height, the greater the time interval for extubation (P=0.034). Pulmonary hypertension, in turn, had no influence on the time interval for extubation (P=0.397) (Table 7).

Table 6. Perioperative - Homogeneity of groups. Variables

Spinal analgesia

Yes No

Surgery time (min) CPB time (min) Aortic clamping time (min)

GI (without PH) 5 24% 16 76%

Groups

GII (with PH) 3 16% 16 84%

P-value

0.698

158.0 48.0 35.0

[120.0; 180.0] [39.0; 63.0] [28.0; 48.0]

150.0 51.0 38.0

[128.0;170.0] [43.5; 63.0] [34.0; 42.5]

0.674 0.386 0.255

Use of dobutamine

Yes No

2 19

10% 90%

6 13

32% 68%

0.120

Use of sodium nitroprusside

Yes No

17 4

81% 19%

14 5

74% 26%

0.712

Extubation in the operating room

Yes No

21 0

100% 0%

19 0

100% 0%

18.0

[10.0; 22.0]

17,0

[13.5; 21.0]

0.776 0.488

∆T extubation (min) Reintubation

Yes No

0 21

0% 100%

2 17

10% 90%

Deaths in hospital

Yes No

0 21

0% 100%

0 19

0% 100%

For categorical variables were presented absolute and relative frequency and for quantitative variables was presented Q2 [Q1; Q3]. PH=pulmonary hypertension; CPB=cardiopulmonary bypass; ∆T extubation=time interval for extubation (time between turning off the halogenated gas and patient's extubation); min=minutes

Table 7. ∆T extubation - multivariate regression Log-Linear Stepwise. Group = GII Height (m)

P value 0.397 0.034

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exp(β) 0.90 0.99

CI - 95% [0.70; 1.15] [0.97; 1.00]


Silva PS, et al. - Evaluation of the influence of pulmonary hypertension in ultra-fast-track anesthesia technique in adult patients undergoing cardiac surgery

Braz J Cardiovasc Surg 2015;30(4):449-58

In GII there were 2 patients who were reintubated in the first 24 hours postoperatively; however, with no statistical difference when compared to GI (P=0.488). No variable influenced the reintubation. This finding was mainly due to the small sample size (Table 8).

nary artery bypass graft (CABG), but these were excluded for not using CPB. The results found in this study was similar to other cardiac surgery services in sub-Saharan Africa in terms of patient characteristics and operated pathologies, where rheumatic fever is highly prevalent, and is a major cause of valve disease with surgical need in young adults[15-17]. The coronary diseases are uncommon in this population, probably due to low life expectation. Borraci et al.[18] analyzing the causes of failure in UFTA in coronary artery bypass graft surgery (CABG), valve or combined, observed that the factors that may predict difficulty of extubation in the operating room in surgery with

DISCUSSION This study assessed young adults, predominantly female, with few comorbidities, with low to moderate cardiovascular risk, mostly affected by heart valve disease with prevalence of mitral valve disease. Only two patients underwent coroTable 8. Reintubation. Variables Group

GI GII

21 17

Gender

Female Male

Age (years) Weight (kg) Height (m)

No

Yes

0% 100%

P-value

55% 45%

0 2

24 14

63% 37%

1 1

50% 50%

1.000

33 50 1.6

[21.0; 44.0] [45.0; 59.5] [1.5; 1.7]

29.5 50.5 1.7

[22.0; 37.0] [35.0; 66.0] [1.5; 1.9]

0.803 0.733 0.514

0.488

SAH

No Yes

29 9

76.30% 23.70%

2 0

100.00% 0.00%

1.000

Smoking

No Yes

34 4

89.50% 10.50%

2 0

100.00% 0.00%

1.000

60

[60; 70]

50

[50; 60]

0.162

Low Medium High

27 10 1

71% 26% 3%

1 1 0

50% 50% 0%

0.515

No Yes

30 8

79% 21%

2 0

100% 0%

1.000

Surgery time (min)

152.5

[120.0; 176.0]

207,5

[140.0; 275.0]

0.368

CPB time (min)

49.5

[40.0; 63.0]

77

[48.0; 106.0]

0.321

Aortic clamping time (min)

36.5

[30.0; 43.0]

55.5

[28.0; 83.0]

0.756

LVEF (%) EuroSCORE

Spinal analgesia

Dobutamine

No Yes

31 7

81.60% 18.40%

1 1

50.00% 50.00%

0.364

Sodium nitroprusside

No Yes

8 30

21.10% 78.90%

1 1

50.00% 50.00%

0.404

16.5

[10.0; 22.0]

19.5

[18.0; 21.0]

0.576

∆T extubation (min)

For categorical variables were presented absolute and relative frequency and for quantitative variables was presented Q2 [Q1; Q3]. SAH=siystemic arterial hypertension; LVEF=left ventricular ejection fraction; CPB=cardiopulmonary bypass

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cardiopulmonary bypass (CPB) are: heart failure, left ventricular dysfunction, emergency surgery, prolonged time of aortic clamping, difficulty to exit CPB and the need for pacemaker use; and in surgeries without CPB: lung disease, obesity, emergency surgery, the need for pacemaker use and hemodynamic instability. Dáyan et al.[19] cited as possible causes of failure of UFTA: female gender, obesity and a history of cardiac failure. Royse et al.[20] reported severe pulmonary hypertension as a cause of failure in one of its UFTA pacientes. Vida et al.[21], on the other hand, analyzing children, concluded that PH does not contraindicate early extubation. Rady et al.[22], in a cohort study of 11,330 patients admitted to the ICU, analyzing the causes of extubation failure (requiring reintubation and mechanical ventilation), cited, among other causes, PH. All study patients were extubated in the operating room. No single factor led to extubation failure. The sPAP in the GII ranged 44-121 mmHg, and even patients with severe HP were extubated, so that the PH had no influence at the time of extubation. Most studies with extubation in operating room in adults were performed in patients undergoing off-pump surgery. If we consider the majority of the available studies involving patients undergoing on-pump and off-pump surgery, extubation rate in the operating room varies from 42 to 100%. Some authors cite the time to extubation ranging between 10 and 20 minutes after skin closure, others mention only the patients who were extubated[3,7-9,18,19]. Only two studies in the literature involving surgery with CPB in adults showed rate of 100% immediate extubation. The study by Hermmeling et al.[8] with 45 patients who were extubated within 15 minutes of the end of the surgery, in which balanced anesthesia was used with a low dose of fentanyl and maintenance with sevoflurane and the study of Oxelbark et al.[9] with 250 consecutive patients, all of which being extubated within 10 minutes from skin closure. In the latter study total intravenous anesthesia with propofol and remifentanil was used. In both cases thoracic epidural analgesia (TEA) was performed. Neither studies report PH as an aggravating factor. In another study by Hermmeling et al.[23] in patients operated without CPB and TEA, undergoing UFTA, compared the effects of isoflurane and sevoflurane between two groups of patients. There was no difference in terms of myocardial protection, cardiac contractility and hemodynamic stability, but the time to extubation was significantly lower in the group using sevoflurane (10±5 minutes) compared to the group using isoflurane (18±4 minutes). Extubation rate in our study was 100%, with an average time interval for extubation of 17.58±8.06 min, with a median of 18 min in GI and 17 min in GII - no statistical difference between the two groups. PH had no influence on the time interval for extubation of patients. We believe that the fact that we used as halogenated isoflurane may have been

the cause of a slightly longer time for extubation compared to studies by Hermmeling et al.[8] and Oxelbark et al.[9] In the present study TEA was not performed, analgesia was performed with spinal morphine (in 8 patients) associated with venous analgesia or only venous analgesia, and this factor had no influence on UFTA. The height of the patients, even after multivariate analysis, showed to have had influence on the time interval for extubation, and the lower the height, the greater the time interval for extubation. We did not find in literature studies mentioning short stature as the only factor in the increase of time for extubation. In the first 24 hours after surgery, 2 patients of GII required reintubation, representing 5% of patients. The reintubation rate presented in the study is within the range reported in the literature in UFTA ranging 0 to 8%[7-9,18,19,23]. There was no statistical difference between the two groups. PH and any other factor influenced the reintubation. When assessing the causes of reintubation of two patients, one was reintubated by CO2 retention and another was reintubated due to seizure followed by cardiorespiratory arrest (CPA). The first patient was extubated again one hour later and the second after 24 hours of intubation. It was found in the history of the first patient that he had important area of pulmonary fibrosis due to tuberculosis sequel, frequent pathology in developing countries in Africa. This may have been responsible for respiratory complication of this patient in the PO and likely because of his reintubation. The opening of the left chambers in cardiac surgery predisposes to gas embolism, which we believe have been the cause of the seizure of the latter patient, since it had no history of seizures before surgery. The major causes of reintubation in UFTA cited in the literature are: respiratory depression and bleeding[18,19]. The seizure has not been among them. We suggest giving special importance to the history of pulmonary disease in patients eligible for UFTA and the patients carriers of such disease should perhaps be referred under intubation to ICU, and consider the time of heart deaeration (removal of intracardiac air) as a surgical time to be respected, in order to avoid postoperative complications leading to reintubation. The sPAP of reintubated patients was 48 mmHg in the patient who presented CO2 retention and 47 mmHg in the patient reintubated for seizure followed by CPA. We believe that the reintubation of these patients is not related to their PH, but with tuberculous lung of the first patient and postoperative complication of the second one. Some authors claim that PH is an important risk factor for intraoperative morbidity and mortality[12]. In the present study, although the patients have presented some degree of intraoperative morbidity, there were no deaths during surgery or in the postoperative period. We consider the main limitation of this study the small number of patients, being necessary to the future, to perform

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studies with a larger population in order to generate a more solid evidence on the subject.

7. Walji S, Peterson RJ, Neis P, DuBroff R, Gray WA, Benge W. Ultra-fast track hospital discharge using conventional cardiac surgical techniques. Ann Thorac Surg. 1999;67(2):363-9.

CONCLUSION

8. Hemmerling TM, Lê N, Olivier JF, Choinière JL, Basile F, Prieto I. Immediate extubation after aortic valve surgery using high thoracic epidural analgesia or opioid based analgesia. J Cardiothorac Vasc Anesth. 2005;19(2):176-81.

PH had no influence on UFTA in adult heart surgery, because it did not preclude the extubation in the operating room, it did not increase the time interval for extubation and it was not cause of reintubation of patients in the first 24 hours postoperatively. In the population studied pulmonary hypertension had no effect on in-hospital mortality.

9. Oxelbark S, Bengtsson L, Eggersen M, Kopp J, Pedersen J, Sanchez R. Fast track as a routine for open heart surgery. Eur J Cardiothorac Surg. 2001;19(4):460-3. 10. Abuchaim DC, Bervanger S, Medeiros SA, Abuchaim JS, Burger M, Faraco DL. Early extubation in the operating room in children after cardiac surgery. Rev Bras Cir Cardiovasc. 2010;25(1):103-8.

Authors’ roles & responsibilities PSS

MPTC CCC MFSF ACAB

Analysis and/or interpretation of data; final approval of the manuscript; Conception and study design; Implementation of projects and/or experiments; manuscript writing or critical review of its contents Study design; collection, analysis and interpretation of data Data collection Analysis and interpretation of data; manuscript writing Manuscript writing

11. Gangopadhyay S, Acharjee A, Nayak SK, Dawn S, Piplai G, Gupta K. Immediate extubation versus standard postoperative ventilation: Our experience in on pump open heart surgery. Indian J Anaesth. 2010;54(6):525-30. 12. Gille J, Seyfarth HJ, Gerlach S, Malcharek M, Czeslick E, Sablotzki A. Perioperative anesthesiological management of patients with pulmonary hypertension. Anesthesiol Res Pract. 2012;2012:356982. 13. Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al.; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension. Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009;30(20):2493-537.

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18. Borracci RA, Dayan R, Rubio M, Axelrud G, Ochoa G, Rodríguez LD. Factores asociados a falla de extubación inmediata en el quirófano después de cirugía cardíaca con y sin circulación extracorpórea. Arch Cardiol Mex. 2006;76(4):383-9.

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19. Dayán R, Borracci RA, Rubio M, De Simón E. La extubación inmediata en el quirófano como conducta de primera elección después de cirugía cardíaca en adultos. Rev Arg Anest. 2005;63:82-90.

22. Rady MY, Ryan T. Perioperative predictors of extubation failure and the effect on clinical outcome after cardiac surgery. Crit Care Med. 1999;27(2):340-7. 23. Hemmerling T, Olivier JF, Le N, Prieto I, Bracco D. Myocardial protection by isoflurane vs. sevoflurane in ultra-fast-track anaesthesia for off-pump aortocoronary bypass grafting. Eur J Anaesthesiol. 2008;25(3):230-6.

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Erdem O, et al. - Effects of intraoperative ORIGINAL ARTICLE diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery

Effects of intraoperative diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery Efeitos da infusão intraoperatória de diltiazem sobre as mudanças do fluxo em enxertos arteriais e venosos em cirurgia de revascularização do miocárdio

Ozan Erdem1, MD; Mehmet Erdem Memetoğlu1, MD, PhD; Ali İhsan Tekin1, MD; Ümit Arslan1, MD; Özgür Akkaya1, MD; Rasim Kutlu2, MD, PhD; İlhan Gölbaşı1, MD; PhD

DOI: 10.5935/1678-9741.20150045

RBCCV 44205-1664

Abstract Objective: This study aimed to show the effects of intra-operative diltiazem infusion on flow in arterial and venous grafts in coronary artery bypass graft surgery. Methods: Hundred fourty patients with a total of 361 grafts [205 (57%) arterial and 156 (43%) venous] underwent isolated coronary surgery. All the grafts were measured by intraoperative transit time flow meter intra-operatively. Group A (n=70) consisted of patients who received diltiazem infusion (dose of 2.5 microgram/kg/min), and Group B (n=70) didn’t receive diltiazem infusion. Results: Mean graft flow values of left internal mammary artery were 53 ml/min in Group A and 40 ml/min in Group B (P<0.001). Pulsatility index (PI) values of left internal mammary artery for Group A and Group B were 2.6 and 3.0 respectively (P<0.001). No statistically significant difference was found between venous graft parameters. Conclusion: We recommend an effect of diltiazem infusion in increasing graft flows in coronary artery bypass graft operations.

Resumo Objetivo: Este estudo teve como objetivo mostrar os efeitos da infusão de diltiazem intraoperatória no fluxo arterial e enxertos venosos em cirurgia de revascularização do miocárdio. Métodos: Cento e quarenta pacientes com um total de 361 enxertos [205 (57%) arteriais e 156 (43%) venosos] passaram por uma cirurgia coronária isolada. Todos os enxertos foram medidos pelo medidor de fluxo de tempo de trânsito intraoperatório. Grupo A (n=70), formado por pacientes que receberam infusão de diltiazem (dose de 2,5 micrograma/kg/min), e Grupo B (n=70), por aqueles que não receberam infusão de diltiazem. Resultados: Os valores médios de fluxo de enxerto de artéria mamária interna esquerda foram 53 ml/min no grupo A e 40 ml/min no Grupo B (P<0,001). Valores do índice de pulsatilidade da artéria mamária interna esquerda para o Grupo A e do Grupo B foram de 2,6 e 3,0, respectivamente (P<0,001). Não houve diferença estatisticamente significativa entre os parâmetros do enxerto venoso. Conclusão: Sugerimos um efeito da infusão de diltiazem em aumentar os fluxos de enxerto em operações de bypass de artéria coronária.

Descriptors: Flow Measurements. Coronary Artery Bypass. Diltiazem. Myocardial Revascularization.

Descritores: Medição de Vazão. Ponte de Artéria Coronária. Diltiazem. Revascularização Miocárdica.

Akdeniz University School of Medicine, Antalya, Turkey. Denizli State Hospital, Denizli, Turkey.

Correspondence Address: Mehmet Erdem Memetoğlu Akdeniz University School of Medicine/Department of Cardiovascular Surgery DumlupÄnar Boulevard, 07058 - Antalya Campus, Antalya, Turkey E-mail: dr.m.erdem07@hotmail.com

1 2

This study carried out at Akdeniz University School of Medicine, Antalya, Turkey. No financial support. No conflict of interest.

Article received on May 5th, 2015 Article accepted on June 22nd, 2015

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used to assess early graft function and to predict graft error in CABG, thus allowing for prompt revision of anastomotic imperfection and prevent graft failure[5]. Diltiazem is a benzothiazepine Ca channel blocker that can be used alone or in combination for the treatment of hypertension (HT), angina and Prinzmetal angina and acts by blocking Ca afflux in myocardium and smooth muscle cells of vessels. It prevents extracellular Ca afflux between target cells, decreases intracellular calcium and produces dilatation in systemic arteries[6]. In our study, we aimed to measure the effect of diltiazem in intraoperative graft flows using a quantitative method [transit-time flowmetry (TTF) technique], and to assess the predictive value of measured graft flows on in-hospital postoperative outcomes.

Abbreviations, acronyms & symbols ACT COPD CPB CVICU DF IMA KCl LAD LIMA MI NTG PI Qmean RA SVG TTF TTFM

Activated coagulation time Chronic Obstructive Pulmonary Disease Coronary artery bypass graft Cardiovascular intensive care unit Diastolic filling Internal mammary artery Potassium chloride Left anterior descending artery Left internal mammary artery Myocardial infarction Nitroglycerin Pulsatility index Mean graft flow Radial artery Vena saphenous vein graft Transit-time flowmetry Transit time flow meter

METHODS Patients with coronary artery disease who underwent surgery in our clinic between March and July 2013 were included in this prospective, randomized study. This study was approved by the Ethics Committee before initiation. Consent was obtained from the subjects for participation in the study in line with World Medical Association Declaration of Helsinki (World Medicine Assembly, 2004 Tokyo, Japan). Coronary artery bypass graft surgery was performed in the patients in accordance with the coronary artery bypass surgical revascularization indications established by ACC/AHA. In this study, 140 patients underwent isolated coronary surgery with a total of 361 grafts. All the grafts that are operated were measured by TTFM intra-operatively, among which 205 were arterial and 156 were venous. Age range was 36-81 (mean=59.8). 109 (78%) of the patients were male and 31 (22%) were female. Flow waves, mean graft flow (Qmean) and Pulsatility index (PI) were used to consider graft as patent. Poor ventricular function (ejection fraction ≤ 40%), resting sinusal bradycardia (<55 beat/min), left bundle branch block were the preoperative exclusion criteria. Hemodynamically unstable patients who required infusion of study drugs beyond the ranges of our study protocol, off-pump CABG, valve and additional aortic and non-cardiac surgery were also excluded intra-operatively. Risk classification was performed using the EuroSCORE scale[7] created for surgical risk assessment. Demographic data were evaluated including age, EuroSCORE scale, gender, hypertension, smoking, ejection fraction, diabetes mellitus, the use of intra-aortic balloon pump, peripheral arterial disease, chronic renal failure, chronic obstructive pulmonary disease, previous myocardial infarction (MI), and emergency surgery. The subjects were divided into two groups; Group A (n=70) consisting of patients who received diltiazem infusion following anesthesia induction and intubation, and Group B (n=70) consisting of patients who didn’t receive

INTRODUCTION Owing to technological developments and novel techniques, coronary artery bypass graft (CABG) surgery is successfully performed in many centers. The human internal mammary artery (IMA) is commonly used as a coronary graft in CABG surgery due to its superior graft patency and increased long-term survival[1]. Graft spasm of the IMA is a long recognized problem, and vasospasm that may develop in arterial grafts during or after the surgery plays an important role in early postoperative mortality and morbidity through impaired myocardial contraction and low output[2]. Despite extensive investigations on the antispastic therapy in the past decades, IMA spasm sometimes still occurs even in the current practice. The mechanism of graft vasospasm is still unclear and many mechanisms can trigger intraoperative and postoperative vasospasm; factors including surgical stimulus, techniques used to remove the graft, or use of distal IMA segment as well as the effect of several mediators released into the circulation due to ischemic reperfusion damage that may result from the removal of cross clamp during cardio-pulmonary bypass (CPB) are involved in the development of vasospasm. Furthermore, reversal and prevention of graft vasospasm are often challenging and the most effective therapy to overcome spasm is still controversial. Intraoperative transit time flow meter (TTFM) has been widely used to evaluate graft patency in CABG[3]. Compared with other methods for graft blood flow measurement, intraoperative TTFM is non-invasive, easy to use, reproducible and provides real-time information about the haemodynamic characteristics of constructed grafts[4]. The TTFM can be

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diltiazem infusion. Diltiazem was given at a dose of 2.5 microgram/kg/min (Diltizem-L, Mustafa Nevzat Pharmaceuticals, İstanbul, Turkey).

Transit time flow measurement Flow measurement was performed using a transit time flow meter (MediStim VeriQ System, Norway) after all anastomoses were completed and haemodynamic parameters, such as blood pressure and heart rate, became stable. Based on graft diameter, either 3 or 4 mm, a flow probe was used for flow measurement. Measurements were performed from the distal part of the graft and before sternum closure, and flow parameters recorded included Q mean, PI and diastolic filling (DF). Mean arterial pressure was strictly adjusted at 70-90 mmHg during measurements. Gel may be used during short segment IMA measurements to decrease the interposition between the vessel and the tissue and to increase probe-vessel relation. Before the measurements, blood flow was increased by restoring the normal position of the heart by removing pericardial suspenders.

Surgical Procedure The left IMA (LIMA) was dissected following median sternotomy. Distal IMA was divided under bleeding control before musculophrenic and superior epigastric branches, and prepared as graft with external administration of papaverine. Radial artery (RA) and right vena saphenous vein graft (SVG) were prepared from non-dominant limbs in eligible patients simultaneously with IMA dissection. The possibility of postoperative extremity ischemia was eliminated using modified Allen test before RA dissection. A three-hundred unit/kg heparin was intravenously administered to maintain activated coagulation time (ACT) over 400 seconds. When this level was achieved, aorta and right atrium were cannulated. The patients were cooled down to 30-32°C and cross clamp was placed. Extracorporeal circulation was established by roller pump (Sarns 9000 perfusion systems, Ann Arbor, Michigan USA) and membrane oxygenator (Sechrist 3500 HL, Anaheim USA). Pump prime solution was prepared using 1500 ml of Ringer Lactate, 150 ml of 20% mannitol and 60 ml of sodium bicarbonate. Keeping the mean arterial pressure at 50-60 mmHg, pump flow was adjusted at 2.2-2.4 l/m2/ min. Perfusion was continued in both groups so that hematocrit value would be over 25%. A three-step cardioplegia was performed to protect myocardium. Following the cross clamp placement, 500 ml of normothermic blood cardioplegia was administered. The Ringer Lactate/blood content of normothermic blood cardioplegia was adjusted as 1:4. Then, topical cooling was administered with Ringer’s lactate solution at 4°C while 10 ml/kg cold crystalloid cardioplegia (St.Thomas sol.) was given at a mean pressure of 40 mmHg. The final cardioplegia was given as a 500 ml of hot shot blood cardioplegia immediately before the cross clamp removal. Distal coronary anastomoses were performed with 7/0 propylene material and proximal anastomoses with 6/0 propylene using continues suture technique. Proximal radial artery and saphenous vein anastomosis were done to aorta. Cross clamp was removed after distal anastomoses were finished and proximal anastomoses were performed under side clamp practice. No hemofiltration was used. Bleeding was controlled at the surgery area after heparin effect was antagonized by protamine. Measurements were performed from the distal part of the graft and before sternum closure and recorded while taking into consideration Qmean, PI and diastolic filling (DF). The patients were taken to cardiovascular surgery intensive care unit after surgery. They were connected to ventilation and DII standard electrocardiogram, arterial pulse oximetry, arterial blood pressure and central venous pressure were monitored.

Evaluation criteria for satisfactory anastomosis Anastomotic patency was considered satisfactory when the following criteria were met: (i) waveform of blood flow is normal and satisfactory. Blood filling is diastolic dominant. A DF value is >50 %, which is consistent with the characteristics of coronary artery blood flow. (ii) PI is acceptable (<5)[8]. Failure to meet either of the criteria indicated an anastomotic defect and required an immediate revision. All postoperative cardiac surgery patients were taken to a cardiovascular intensive care unit (CVICU). Patients discharged from the CVICU were transferred to a general care ward under the care of the same team. All patients were monitored continuously for a minimum of 24 h. Postoperative parameters for investigation were as follows: need for revision, prolonged intubation, atrial fibrillation (AF), postoperative early myocardial infarction, postoperative development of acute renal failure and need for hemodialysis, neurological complications, time spent in intensive care and in-hospital mortality. Statistics Data was given as mean ± standard deviation. The significance of demographic and clinical statistical difference between groups was evaluated using Student T test, Mann Whitney U test and Chi square tests. P values lower than 0.05 were considered significant. No significant difference was found between the groups in terms of demographic characteristics. RESULTS The study consisted of 140 patients underwent coronary surgery with a total of 361 grafts. All the grafts that are operated were measured by TTF intraoperatively, among which 205 were arterial and 156 were venous. Age range was 36-81 (mean=59.8). 109 (78%) of the patients were male and 31 (22%) were female.

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In Group A, infusion with diltiazem was started in this group of patients following anesthesia induction and intubation. In Group A, a total of 202 grafts were performed in 70 patients [69 (34%) LIMA, 63 (31%) saphenous vein, 70 (34%) radial artery], 43 (61%) of the patients were male and 27 (39%) were female. A total of 70 patients, 66 (94%) male and 4 (6%) female were evaluated. Age range was 36-78 with an average of 57. In Group B, a total of 159 grafts were performed in 70 patients [66 (42%) LIMA, 93 (58%) saphenous vein, 43 (61%) of the patients were male and 27 (39%) were female. Age range was 53-81 with an average of 64.7]. The mean cardiopulmonary bypass time for Group A was 121.8±20.5 and 125±24.3 for Group B (minute, P=0.32).

Comparison of the basal charecterictics, preoperative echocardiografic and clinical parameters among patients for Group A and Group B are shown in Table 1. Number of anastomoses, Q mean, and PI and DF values for Group A and Group B patients are shown in Table 2. In both Group A and B, LIMA-left anterior descending artery (LAD) anostomosis was performed in 69 patients, while LAD anastomosis was performed in one patient by using SVG because of the inconvenience of LIMA. The detailed data revealed that the majority of the patients were male in Group A and were statistically different (P<0.001). Smoking was statistically significantly more common in Group A compared to Group B.

Table 1. Comparison of the basal charecterictics, preoperative echocardiografic and clinical parameters among patients from Group A and Group B. Preoperative Parameters Age EuroSCORE Gender Hypertension Smoking Diabetes Mellitus Ejection Fraction (EF) Intraaortic Balloon Pump (IABP) Peripheral Artery Disease Chronic Renal Failure Chronic Obstructive Pulmonary Disease Myocardial Infarction Urgent Operation

Group A 57 1.5 K: %6 (4) E: %94(66) %60 (42) %70 (49) %37 (26) 58 3 %4 (3) %2 (1) %19 (13) %25 (18) %2 (1)

Group B 64.7 2.7 K: %38 (27) E: %62 (43) %56 (39) %53 (37) %31 (22) 59 8 %10 (7) %10 (7) %24 (17) %35 (25) %4 (3)

P P>0.05 P>0.05 P<0.001 P>0.05 P<0.037 P>0.05 P>0.05 P>0.05 P>0.05 P>0.05 P>0.05 P>0.05 P>0.05

Table 2. Number, mean graft flow, diastolic filling, and pulsatile index values for Group A and Group B patients. Group A LIMA-LAD RA-OM1 RA-RCA SVG-LAD SVG-DIAG SVG-OM1 SVG-RCA Group B LIMA-LAD SVG-LAD SVG-DIAG SVG-OM1 SVG-RCA

Number 69 60 10 1 10 11 41 Number 69 1 11 43 38

Qmean 53 50 52 63 34 44 52 Qmean 40 8 39 45 65

PI 2.6 2.3 2.0 1.5 2.1 2.7 2.7 PI 3.0 4.5 2.4 3.3 2.8

DF 69 65 64 69 71 62 63 DF 66 55 71 66 61

LIMA=left Internal Mammary Artery; LAD=left anterior descending artery; RA=radial artery; OM=obtuse marginal; SVG=saphenous vein graft; DIAG=diagonal artery; RCA=right coronary artery; Q mean=mean graft flow; DF=diastolic filling; PI=pulsatile index

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In a comparison between Group A and B, no difference was seen with respect to age, EuroSCORE, hypertension, diabetes mellitus, ejection fraction, peripheral arterial disease, chronic renal failure, Chronic Obstructive Pulmonary Disease (COPD), previous MI and emergency surgery. All the arterial and venous grafts in both groups were recorded by measuring with TTF, and compared for Qmean, PI and DF values. Qmean and PI values were compared for IMA anastomoses, and a significant increase was found in Group A (P<0.001) (Table 3). No significant difference was observed in the flow measurements in venous graft anastomoses. Among postoperative follow-up parameters, only the development of atrial fibrillation was significantly different in Group A (6 patients) compared to Group B (16 patients) (P<0.020). Other parameters did not show any difference (Table 4).

not clearly defined. Many theories have been proposed including techniques used to remove the arterial graft, inappropriate manipulations for the graft, over activation of Ca channels, increase in alpha-adrenergic activity, high blood pH, low body temperature, increased vasopressin levels, excessive release of histamine, low PaCO2, use of distal 1/3 part of IMA for anostomosis and smoking[9,10]. In addition, accumulation of depolarizing agents as KCl (potassium chloride), free radicals induced by alpha-adrenergic receptors, and increase in agents as arginine or vasopressine also play role in vasospasm[11]. In recent years, arterial grafts other than IMA have become prominent since long term occlusion rates are high with saphenous vein. The most commonly used is the RA. Despite their high rate of staying patent, the most important problem when using arterial grafts is their susceptibility to vasospasm during perioperative period. In a meta-analysis issued by Wijeysundera & Beattie[12], it was demonstrated that intraoperative use of diltiazem reduces the incidence of ischemia and supraventricular tachycardia, while being useful in reducing death and myocardial infarction in postoperative period. Since vasospasm is induced by various pathways, generation of a synergic effect through simultaneous inhibition of different pathways by using Ca channel blockers and Nitroglycerin (NTG) concomitantly has been studied. Chanda et al.[13] reported that concomitant use of diltiazem and NTG results in better outcomes in loosening of the contraction compared to when each drug is used alone. Lemmer et al. reported in their study that intracoronary infusion of nitroglycerin had a beneficial effect in the loosening of vasospasm when used together with calcium channel blockers and that Ca channel blockers would have a beneficial effect on ventricular dysfunction[14]. In the study of Tabel et al.[15], half of the patients undergoing elective CABG were given diltiazem and the other half was given NTG together with anesthesia induction. Two measurements had been taken. First, free flow value was measured after IMA was cut from bifurcation level. Then, the second flow measurement was performed after the distal segment was resected. The flow values were found to be 53.8 ml/min in the first measurement and 72.3 ml/min in the second in diltiazem group while the same values were 25.7 ml/min and 48.9 ml/ min, respectively, in NTG group (P=0.000, 0.004, respectively). After the resection of distal segment, both agents increased the flow (P=0.000, 0.000). However, they reported that diltiazem was more effective in preventing IMA spasm. In our study, the flow value in LIMA-LAD graft was 53 ml/min in the group that were given diltiazem and 40 ml/min in the group without diltiazem (P<0.001). Inokuchi et al.[16] reported that fasudil, a Rho-kinase inhibitor, is effective in suppressing coronary artery spasm in patients with vasospastic angina. The IMA flow can be increased by administering vasodilators such as Ca channel blockers, long acting nitrates and

Table 3. The Qmean and PI values compared for IMA anastomoses in Group A and B. Grafts LIMA - LAD (Q mean) LIMA - LAD (P)

Group A (n=69) 53 ml/min 2.6

Group B (n=66) 40 ml/min 3

P value <0.001 <0.001

LIMA=left internal mammary artery; LAD=left anterior descending artery; Q mean=mean graft flow; PI=pulsatile index Table 4. Comparison of number of Group A and Group B patients according to postoperative parameters. Need for Revision Prolonged Intubation Atrial Fibrillation Postop MI Postop HD Peripheral Embolus Neurologic Complication Duration of Intensive Care Mortality

Group A 4 6 6 0 1 0 3 4 0

Group B 4 10 16 0 7 0 2 3.3 4

P value >0.05 >0.05 <0.020 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05

MI=myocardial infarction; HD=hemodialysis; Postop=postoperative

DISCUSSION In this study, by using intraoperative TTFM, it was observed a statistically significant increase in arterial graft flows intraoperatively, and a lower incidence of atrial fibrillation during intra- and postoperative periods in the group that was given diltiazem. Coronary artery spasm and the arterial graft that occurs during and early after coronary artery surgery can result in a sudden and severe cardiopulmonary failure. The mechanisms underlying intraoperative and postoperative vasospasm are

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phosphodiesterase inhibitors during surgery. Otherwise, this condition is associated with high mortality and morbidity. However, these agents are rather effective in decreasing graft spasm than their vasodilator effect. Apart from its effect on vasospasm, we discovered in our study that intraoperative use of diltiazem also reduces the development of atrial fibrillation. There was a statistically significant decrease compared to the other group (P<0.02). Besides its effect on arrhythmia, ventricle protecting and anti-ischemic effects have also been reported in the literature. In a double blind, randomized study of Zhang et al.[17] on 71 elective CABG patients, diltiazem infusion provided a better protection against both ischemia and supraventricular arrhythmia. It was also reported that preoperative diltiazem was effective in reducing arrhythmia and transient ischemic events in addition to prevention of IMA spasm[18]. The predicted blood flow through LIMA-LAD graft is 25-50 ml/min[19]. This value is higher in venous grafts. That is because IMA cannot get adapted to the sudden decrease in the peripheral vascular resistance and increasing outflow. However, graft measurements in one year have shown a doubled amount in blood flow. In the past, a number of methods had also been used to measure graft patency. Much better results have been reported with intraoperative TTF[20]. Perioperative flow measurement protects the patient from unjustifiable complications and provides the surgeon with patency of the graft. We consider that use of TTF in CABG is important in order to achieve a high success and low mortality/morbidity. TTF measurement is fast, economic, effective and is a simple alternative that helps the surgeon compared to methods as CAG. Abnormal flow was seen in five of the grafts and revision was performed. We considered a possible anastomosis error in five patients because of various reasons when all three parameters were assessed. All of these parameters recovered when the anostomoses were fixed. Thus, we protected the patients from any postoperative complications. The present study has several limitations. First of all, this study is not “surgeon-blind”, and the control group did not fully reflect features of the study group. The number of patients who were included in the study was another limitation of our study. Although we adjusted for many clinical and procedural characteristics, hidden confounders cannot be excluded, we did not measure other markers of specific oxidative stress and inflammation which may be associated with vasospasm, such as free radical levels. In the studies, long term benefits were demonstrated for arterial grafts used in coronary revascularization. Other studies should be performed in the future in order to understand the reasons and prevent arterial graft spasm which is the most important problem during intraoperative and early preoperative period. In these studies, the novel techniques and treatment modes developed to prevent

vasospasm will contribute to the reduction of mortality and morbidity of future CABG surgery. CONCLUSION In conclusion, the beneficial effect of diltiazem on LIMA flows in patients undergoing CABG surgery was found in this study, we therefore recommend diltiazem infusion in increasing LIMA graft flows. Authors’ roles & responsibilities OE MEM AIT ÜA ÖK RK IG

Analysis and/or interpretation of data; final manuscript approval; implementation of projects and/or experiments Analysis and/or interpretation of data; final manuscript approval; implementation of projects and/or experiments Analysis and/or interpretation of data; study design; implementation of projects and/or experiments Conduct of operations and/or experiments Analysis and/or interpretation of data; implementation of projects and/or experiments Analysis and/or interpretation of data Study conception and design

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8. Yu Y, Yan XL, Wei H, Yang JF, Gu CX. Off-pump sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system. Chin Med J (Engl). 2011;124(19):3017-21.

16. Inokuchi K, Ito A, Fukumoto Y, Matoba T, Shiose A, Nishida T, et al. Usefulness of fasudil, a Rho-kinase inhibitor, to treat intractable severe coronary spasm after coronary artery bypass surgery. J Cardiovasc Pharmacol. 2004;44(3):275-7.

9. Döpfmer UR, Braun JP, Grosse J, Konertz W. Temporary left ventricular assist and levosimendan for coronary artery spasm. Interact Cardiovasc Thorac Surg 2005;4(4):316-8.

17. Zhang P, Chen G, Zhang P, Zheng K, Wang GL. Cardioprotective effects of diltiazem infusion in the perioperative period in patients undergoing coronary artery bypass grafting with extracorporeal circulation. Zhonghua Yi Xue Za Zhi. 2003;83(16):1387-90.

10. Kimura N, Kawahito K, Adachi K, Murata H, Yamaguchi A, Adachi H, et al. Effects of intra-coronary and intra-graft administration of nicorandil for coronary spasm after coronary artery bypass grafting. Kyobu Geka. 2006;59(1):71-7.

18. Hannes W, Seitelberger R, Christoph M, Keilich M, Kulinna C, Holubarsch C, et al. Effect of peri-operative diltiazem on myocardial ischaemia and function in patients receiving mammary artery grafts. Eur Heart J. 1995;16(1):87-93.

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20. Lehnert P, Møller CH, Damgaard S, Gerds TA, Steinbrüchel DA. Transit-time flow measurement as a predictor of coronary bypass graft failure at one year angiographic follow-up. J Card Surg. 2015;30(1):47-52.

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Özülkü M & Aygün F - EffectARTICLE of using pump on postoperative pleural effusion ORIGINAL in the patients that underwent CABG

Effect of using pump on postoperative pleural effusion in the patients that underwent CABG Efeito da circulação extracorpórea no derrame pleural pós-operatório em pacientes submetidos à revascularização do miocárdio

Mehmet Özülkü1, MD; Fatih Aygün1, MD

DOI: 10.5935/1678-9741.20150029

RBCCV 44205-1665

Abstract Objective: The present study investigated effect of using pump on postoperative pleural effusion in patients who underwent coronary artery bypass grafting. Methods: A total of 256 patients who underwent isolated coronary artery bypass grafting surgery in the Cardiovascular Surgery clinic were enrolled in the study. Jostra-Cobe (Model 043213 105, VLC 865, Sweden) heart-lung machine was used in on-pump coronary artery bypass grafting. Off-pump coronary artery bypass grafting was performed using Octopus and Starfish. Proximal anastomoses to the aorta in both on-pump and off-pump techniques were performed by side clamps. The patients were discharged from the hospital between postoperative day 6 and day 11. Results: The incidence of postoperative right pleural effusion and bilateral pleural effusion was found to be higher as a count in Group 1 (on-pump) as compared to Group 2 (off-pump). But the difference was not statistically significant [P>0.05 for right pleural effusion (P=0.893), P>0.05 for bilateral pleural effusion (P=0.780)]. Left pleural effusion was encountered to be lower in Group 2 (off-pump). The difference was found to be statistically significant (P<0.05, P=0.006). Conclusion: Under the light of these results, it can be said that left pleural effusion is less prevalent in the patients that underwent off-pump coronary artery bypass grafting when

compared to the patients that underwent on-pump coronary artery bypass grafting.

Başkent University, Konya Research and Medical Center, Turkey.

Correspondence address: Fatih Aygün Department of Cardiovascular Surgery, Konya Medical and Research Center, Başkent University, Konya Hocacihan Mah. Saray Cad No:1, 42000 Selçuklu-Konya, Turkey E-mail: fatihaygun@ttmail.com

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Descriptors: Coronary Artery Disease. Cardiac Surgical Procedures. Cardiopulmonary Bypass. Pleural Effusion. Coronary Artery Bypass, Off-Pump. Resumo Objetivo: O presente estudo investigou efeito da utilização de bomba em derrame pleural pós-operatório nos casos de pacientes que se submeteram à cirurgia de revascularização miocárdica. Métodos: Um total de 256 pacientes que foram submetidos à cirurgia de revascularização isolada no ambulatório de Cirurgia Cardiovascular foram incluídos no estudo. Máquina coração-pulmão Jostra-Cobe (Modelo 043213 105, VLC 865, Suécia) foi utilizada em cirurgia de revascularização miocárdica com circulação extracorpórea. Cirurgia de revascularização miocárdica sem circulação extracorpórea foi realizada utilizando Octopus e Starfish. Anastomose proximal na aorta, em ambas as técnicas, foi realizada por grampos laterais. Os pacientes receberam alta do hospital entre os dias 6 e 11 de pós-operatório. Resultados: A incidência de derrame pleural à direita pós-operatória e derrame pleural bilateral encontrada foi mais elevada em contagem do Grupo 1 (com circulação extracorpórea)

This study was carried out at Department of Cardiovascular Surgery, Konya Medical and Research Center, Başkent University, Konya, Turkey.

Article received on December 27th, 2014 Article accepted on April 26th, 2015

No financial support.

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Özülkü M & Aygün F - Effect of using pump on postoperative pleural effusion in the patients that underwent CABG

bilateral (P=0,780)]. O derrame pleural esquerdo encontrado foi menor no Grupo 2 (CEC). A diferença foi estatisticamente significativa (P<0,05, P=0,006). Conclusão: Sob a luz destes resultados, pode-se dizer que derrame pleural esquerdo é menos prevalente nos pacientes que foram submetidos à revascularização do miocárdio sem circulação extracorpórea em comparação com os pacientes que foram submetidos à revascularização do miocárdio com circulação extracorpórea.

Abbreviations, acronyms & symbols CABG Coronary artery bypass grafting COPD Chronic obstructive pulmonary disease CAD Coronary artery disease BMI Body mass index ml Milliliter cm Centimeter mm Millimeter

em relação ao Grupo 2 (sem circulação extracorpórea). Mas a diferença não foi estatisticamente significativa [P>0,05 para derrame pleural à direita (P=0,893), P>0,05 para derrame pleural

Descritores: Doença da Artéria Coronariana. Procedimentos Cirúrgicos Cardíacos. Ponte Cardiopulmonar. Derrame Pleural. Ponte de Artéria Coronária sem Circulação Extracorpórea.

INTRODUCTION

METHODS Clinical Characteristics of Patients A total of 256 patients, who underwent isolated CABG surgery in the Cardiovascular Surgery clinic and had no valvular pathology or connective tissue disease (Marfan syndrome, etc.) were enrolled in the study. The data were retrospectively collected. In the preoperative period, all patients were questioned in terms of medical history and underwent detailed physical examination. Standard preoperative laboratory tests were performed in the preoperative period in CVS clinic; pulmonary function test (Spirobank Spirometry, MIR medical International Research Product) was performed in case any pathology was detected in the patients during respiratory system anamnesis or examination, transthoracic echocardiography (TTE) (Acuson, Mountain View, Acuson Sequoia C256) was performed in all patients, and bilateral carotid artery Doppler ultrasonography (Toshiba XARIO prime ultrasound) was performed in the patients with pathology detected on carotid artery and peripheral artery examination as well as in the patients that had lesion in the main coronary artery. Patients were considered as low-weight if body mass index (BMI) was lower than 20 kg/m², normal-weight if BMI was between 20 kg/m² and 24.9 kg/m², over-weight if BMI was between 25 kg/m² and 29.9 kg/m², and obese if BMI was equal to or higher than 30 kg/m². In the preoperative period, clopidogrel (if receiving) therapy was discontinued five days and acetylsalicylic acid therapy was discontinued three days before surgery in the all patients that would undergo On-Pump (with CPB) CABG and OffPump (Beating-heart) CABG.

Coronary artery bypass surgery (CABG) is one of the operations most frequently performed all over the world. Conventional CABG is performed by using cardiopulmonary bypass (CPB) device and called as on-pump CABG, whereas CABG performed without using CPB is called as off-pump CABG. Although postoperative complications are never desirable, they may sometimes be inevitable for some patients. Pleural effusion following CABG is still being encountered despite all efforts of cardiovascular surgeons. It has been reported that pleural effusion occurs in 41%87% of the patients in the postoperative very early period[1-4]. Pleural effusions that occur following coronary bypass surgery can be classified according to the development period as very early period (within postoperative one week) (perioperative), early period (between postoperative one week and one month), late period (between postoperative two and 12 months), and very late period (after postoperative 6 months, permanent)[5]. It is thought that many factors ranging from surgical technique to the preoperative medications have a role on the development of pleural effusion in postoperative early period. Primarily, there are two basic reasons for pleural effusions that occur in the period so-called perioperative period, which comprises postoperative first one-week. The first is diaphragm disorder and the second is harvesting LIMA[6-10]. Heart failure after CABG decreased cardiac output after surgery; pleural infection, pulmonary embolus, and chylothorax are among the causes of postoperative pleural effusion[5,11]. The present study investigated effect of using pump on postoperative pleural effusion in the cases that underwent CABG, as well as the statistical significance of this effect.

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Study Groups The patients that underwent CABG were dichotomized according to two different surgical techniques. The first group (Group 1) consists of patients who underwent CABG by CPB (On-Pump) device. The second group (Group 2) consists of patients who underwent CABG by beating heart (Off-Pump) technique. Proximal anastomoses were performed using side clamps in all patients. Duration of cross-clamping did not exceed 90 minutes and duration of bypass did not exceed 120 minutes in the patients who underwent CABG by CPB cross-clamp technique. All patients underwent surgery by the same surgical team. In order to create a homogeneous group, dialysis patients or the patients with creatinine level over 2 gr/dl, patients with aortic pathology detected during surgery and thereby surgery procedure was changed, patients who had undergone surgery as emergency cases, patients who underwent redo–CABG, patients with postoperative lower respiratory tract infection, patients who developed postoperative diaphragm paralysis, patients who had been re-explored because of drainage, and the patients who died were not included in the study.

Postoperative Care Under normal conditions in the postoperative period, acetylsalicylic acid (Coraspin 300®) was commenced at a dose of 300 mg/day together with enteral nutrition in all patients in order to reduce the risk of complication after CABG. Cefazolin sodium (Cefamezin®-IM/IV), which is used as standard prophylactic antibiotic in our clinic, was administered at a dose of 1gr for once 30 minutes before surgery and then continued for 72 hours after surgery at a dose of 1g at 8 hours intervals. Postoperative blood glucose regulation in diabetic patients was strictly done using insulin glargine 100 IU/ml (Lantus® flacon) and human soluble regular insulin 100 IU/ ml (Humulin-R® flacon). Insulin infusion was not avoided when needed. Blood glucose concentration was kept at the level of 200 mg/dl in all patients. In the postoperative period, the patients stayed at CVS intensive care unit for 48 hours and then they were admitted to the CVS clinic after removing the drains (thoracic and mediastinal drains; they were kept until the drainage became serous and amount of drainage in the last 5 hours was 50 cc) and arterial catheters in the third 24 hours. Central vascular line was removed on the 4th postoperative day in the CVS clinic. The patients were discharged on the 6th-11th postoperative days and checked for pleural effusion on the 7th postoperative day. After they were admitted to the CVS clinic, pleural fluid was controlled with a posteroanterior chest radiography until discharged by 24 hours interval. Patients were evaluated with ultrasonographic costophrenic angle blunting. The patients who presented excessive pleural liquid (500 cc and above) were fitted Pleurocan (8-10French-B. Braun, Melsungen, Germany) If the mount of the fluid taken from the pleural space was 500 cc or above, it was considered as pleural effusion.

Surgical method All patients underwent isolated CABG surgery by cardiopulmonary bypass (CPB) device, beating heart technique or beating heart technique under CPB support. Induction of anesthesia was performed with fentanyl, midazolam and pancuronium bromide. Standard median sternotomy was performed and LIMA and other vascular conduits were prepared before CPB has started. After administering 300 IU/kg heparin, CPB was started by roller pump using standard aortic and two-stage venous cannula. All patients initially received high-potassium crystalloid and then cold standard crystalloid cardioplegia and, at the end, hot-shot cardioplegia during surgery. Whilst the left internal mammary artery (LIMA) was used in all of the cases, the right internal mammary artery was not used. Meticulous aseptic technique was performed in the surgery. Unnecessary use of electro-cautery and unnecessary perfusion in CPB (Luxury) were avoided. Heparinization was performed using 150 IU/kg heparin in the patients who underwent surgery with beating heart technique. Distal anastomoses were performed using Octopus and Starfish. Anastomoses to the aorta were performed using side clamps both in on-pump and off-pump technique. In on-pump or off-pump CABG patients; the left pleura was standardly opened either while preparing LIMA during surgery or just after the LIMA has been prepared. Cold isotonic solution (slash) was used for local cold effect in all onpump CABG patients. The right pleura was opened in all patients who underwent off-pump CABG. At the end of on-off pump CABG procedure, mediastinal and pleural drains were inserted through the subxiphoid area. Inserting mediastinal and left and right pleural drains through the subxiphoid area is a standard procedure in our clinic.

Statistical Analysis Statistical analyses were performed by SPSS program (SPSS Inc., Chicago, IL, USA). Statistical significance of nonparametric data between groups was analyzed by Pearson Chi-Square analysis and Ficher’s Exact Test (it was used because observed values were below the expected values). Parametric data were presented as minimum, maximum and mean±standard deviation and statistical significance of parametric data between the groups was analyzed by independent student t-test. The result was considered significant if twotailed P value is below 0.05 (P<0.05) (Table 1). RESULTS Subjects characteristics Distribution of age of all study participants was minimum (min) 29 years (y) and maximum (max) 89 years (mean±standard deviation 62.6±9.6 y). Of these subjects, 164 (64.1%)

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were male and 92 (35.9%) were female. It was observed that BMI was min 18.3 and max 50.2 (mean±standard deviation 29.6±5) kg/m2. The number of patients with hypertension (HT) was 208 (81.3%) and the number of patients receiving antidiabetic agent was 121 (47.3%). There were 107 (41.8%) smokers and 68 (26.6%) patients with COPD. The number of patients with history of stroke before surgery was 18 (7%), with right pleural effusion was 5 (2%), left pleural effusion was 21 (8.2%), and with bilateral pleural effusion was 20 (7.8%). Among study participants, the number of patients who underwent CABG together with CPB was determined to be 161 (62.8%) and the number of patients who underwent CABG via beating heart technique was determined to be 95 (37.2%). Some data about participants were shown at Table 1 and Table 2.

3 (2.9%), with left pleural effusion was 11 (10.5%), and with bilateral pleural effusion was 8 (7.6%). The mean age (±standard deviation) was 62.2±10.3 y, the mean (±standard deviation) BMI was 28.3±4.6 kg/m2, the mean (±standard deviation) preoperative EF was 52.6±9.42, the mean (±standard deviation) bypass graft performed in CABG was 3.6±0.8, and the number of patients with history of CVA before surgery was 9 (8.6%). It was observed that there were 65 (61.9%) smokers, 81 (77.1%) hypertensive patients, 28 (26.7%) patients with COPD, 7 (6.7%) patients with PAD, 27 (25.7%) patients receiving oral antidiabetic agent and 12 (11.4%) patients receiving parenteral antidiabetic agent. The mean (±standard deviation) preoperative leukocyte count was 8.27±6.2 and the mean (±standard deviation) preoperative thrombocyte count was 248.6±75.4. In the females of Group 1, it was determined that the number of patients with postoperative right pleural effusion was 0 (0%), with left pleural effusion was 8 (14.3%), and with bilateral pleural effusion was 4 (7.1%). The mean age (±standard

Group characteristics In the males of Group 1 it was determined that the number of patients with postoperative right pleural effusion was Table 1. Data according to groups.

Age (±SD) (year) Gender (Male) Smoking COPD Hypertension PAD Preoperative thrombocyte count Preoperative leukocyte count Preoperative stroke history Diabet oral a/d Parenteral a/d Weight (kg) BMI Ejection Fraction

Group 1 ( n=161) (On-pump CABG) 62.8 ±9.6 105 (% 65.2) 70 (% 43.5) 36 (% 22.4) 134 (% 83.2) 9 ( % 5.6) 259.6±90.9 8.14±5.24 11 (% 6.8) 48 (% 29.8) 28 (% 17.4) 78.5±13.4 29.6±5.1 53.8±9.7

Group 2 ( n=95) (Off-pump CABG) 62.2± 9.8 59 (% 62.1) 37 (% 38.9) 32 (% 33.7) 74 (% 77.9) 3 ( % 3.2) 253.8±69.1 8.39±2.15 7 (% 7.4) 30 (% 31.6) 15 (% 15.8) 77.6±12.9 29.8±5 54.6±8.7

P value 0.620T 0.693P 0.478P *0.048P 0.291P 0.544F 0.589T 0.659T 0.871P 0.927P 0.578T 0.784T 0.514T

=P value as Student-t test result; P=P value as Pearson Qi-square test result; F=Fischer’s Exact Test was used because observed values were below the expected values; CABG=coronary artery bypass grafting; COPD=chronic obstructive pulmonary disease; CAD=coronary artery disease; BMI=body mass index T

Table 2. Data according to groups as a postoperative.

Numbers of grafts Pleural Effusion Right Left Bilateral

P value

Group 1 ( n=161) (On-pump CABG) 3.6±0.8

Group 2 ( n=95) (Off-pump CABG) 2.6±0.9

<0.001T

3 (% 1.9) 19 (% 11.8) 12 (% 7.5)

2 (% 2.1) 2 (% 2.1) 8 (% 8.4)

1F *0.008F 0.812F

=P value as Student-t test result; P=P value as Pearson Qi-square test result; F=Fischer’s Exact Test was used because observed values were below the expected values; CABG=coronary artery bypass grafting; COPD=chronic obstructive pulmonary disease; CAD=coronary artery disease; BMI=body mass index T

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deviation) was 64.05±8 y, the mean (±standard deviation) BMI was 31.9±5.1 kg/m2, the mean (±standard deviation) preoperative EF was 56.1±9.9, the mean (±standard deviation) bypass graft performed in CABG was 3.6±0.8, and the number of patients with history of CVA before surgery was determined to be 2 (3.6%). It was observed that there were 5 (8.9%) smokers, 53 (94.6%) hypertensive patients, 8 (14.3%) patients with COPD, 2 (3.6%) patients with PAD, 21 (37.5%) patients receiving oral antidiabetic agent, and 16 (28.6%) patients receiving parenteral antidiabetic agent. The mean (±standard deviation) preoperative leukocyte count was 7.9±2.5 and the mean (±standard deviation) preoperative thrombocyte count was determined to be 280.3±112.5 (Figure 1). In the males of Group 2, it was determined that the number of patients with postoperative right pleural effusion was 1 (1.7%), with left pleural effusion was 1 (1.7%), and with bilateral pleural effusion was 5 (8.5%). The mean (±standard deviation) age was 61.5±9.5 y, the mean (±standard deviation) BMI was 28.1±3.8 kg/m2, the mean (±standard deviation) preoperative EF was 56.3±7.5, the mean (±standard deviation) bypass graft performed in CABG was 2.7±1 and the number of patients with history of CVA before surgery was 5 (8.5%). It was observed that there were 33 (55.9%) smokers, 42 (71.2%) hypertensive patients, 18 (% 30.5) patients with COPD, 2 (3.4%) patients with PAD, 19 (32.2%) patients receiving oral antidiabetic agent and 3 (5.1%) patients

receiving parenteral antidiabetic agent. The mean (±standard deviation) preoperative leukocyte count was 8.5±2.1 and the mean (±standard deviation) preoperative thrombocyte count was 256.7±71.8. In the females of Group 2, it was determined that the number of patients with postoperative right pleural effusion was 1 (2.8%), with left pleural effusion was 11 (2.8%) and with bilateral pleural effusion was 3 (8.3%). The mean (±standard deviation) age was 63.3±10.2 y, the mean (±standard deviation) BMI was 32.4±5.5 kg/m2, the mean (±standard deviation) preoperative EF was 51.8±10, the mean (±standard deviation) bypass graft performed in CABG was 2.5±0.9, and the number of patients with history of CVA before surgery was determined to be 2 (5.6%). It was observed that there were 4 (11.1%) smokers, 32 (88.9%) hypertensive patients, 14 (38.9%) patients with COPD, 1 (2.8%) patient with PAD, 11 (30.6%) patients receiving oral antidiabetic agent, and 12 (33.3%) patients receiving parenteral antidiabetic agent. The mean (±standard deviation) preoperative leukocyte count was 8.2±2 and the mean (±standard deviation) preoperative thrombocyte count was 249±65. The patients were followed until hospital discharge for pleural effusion (very early period). Right pleural effusion was determined in six, left pleural effusion was determined in 21 and bilateral pleural effusion was determined in 20 patients in very early period (Figure 2).

Fig. 1 - Pleural effusion dissociation graphic according to age and body mass index in group 1.

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Fig. 2 - Pleural effusion dissociation graphic according to age and body mass index in group 2.

DISCUSSION

phrenic injury. Our study did not include the patients who present diaphragm paralysis. Pleural effusion may also develop due to congestive heart failure that occurs after CABG[11]. Decrease in cardiac output after surgery may lead to pulmonary edema and bilateral pleural effusion. All of participants in our study have no congestive heart failure. Pleural infection in early period, pulmonary embolus and surgery-related chylothorax as well can be considered among causes of pleural effusion[5]. There are studies demonstrating that some intraoperative techniques reduce pleural effusion. Gullu et al.[12] reported that preserving pleural integrity while harvesting internal mammary artery reduces postoperative pain and the incidence of atelectasis and pleural effusion. It has been emphasized that using LIMA in coronary bypass surgeries enhances effusion as compared to using saphenous vein alone. In our study, LIMA was harvested and left pleural space was opened in all patients. Many researchers including Burgess et al. stated that harvesting ITA (internal thoracic artery) during CABG surgeries increases complications and makes additional contribution to postoperative pulmonary dysfunction[13-15]. Bonacchi et al.[10] indicated chest tube insertion and pleural injury while preparing

Conventional CABG is performed by using cardiopulmonary bypass (CPB) device and called as on-pump CABG, whereas CABG performed without CPB is called as offpump CABG. On-pump CABG is agreed as the gold standard, but this method has some physiological effects. These effects include thrombocytopenia, activation of complement system, immune suppression, and inflammatory response that leads to organ dysfunction. There are two basic causes of perioperative pleural effusion following CABG. The first is pleural effusion due to atelectasis that results from diaphragm dysfunction. It is known that local cold application (slash) during CABG is directly associated with diaphragm paralysis and atelectasis. Correlation has been demonstrated between size of atelectasis and amount of effusion[4]. The second is the pleural effusion due to bleeding that occurs after harvesting internal mamarian artery. Pleural effusion occurs during and after bleeding, which results from trauma to parietal pleura during IMA harvesting. Slash was applied on all participants who underwent on-pump CABG surgery in our study. We tried to escape from adverse effects of slash by using only top of the heart and hood which it is save from

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ITA graft as the reasons for postoperative poor pulmonary function, which seems to support the findings of some researchers[10,13,16,17]. There are studies demonstrating that inserting thoracic drain through intercostal space negatively influence patient comfort in early postoperative period and, in addition, increases the incidence of atelectasis and pleural effusion that occur due to chest wall trauma[16-19]. Contributing to some studies, Wimmer-Greinecker et al. reported that restriction in patient’s movements until the removal of chest tubes causes decrease in pulmonary functions due to restricted inspiratory capacity[17-19]. There are studies stating that inserting subxiphoidal drain for pleural drainage is as effective as intercostal drains. In accordance with our clinical protocol, subxiphoidal chest tube was inserted in all patients aiming at elimination of unfavorable effects of intercostal drains. We had placed the chest tubes at subxiphoidal localization in all surgical procedures. There are publications demonstrating that the incidence of pleural effusion and atelectasis between the 2nd and 5th postoperative days is significantly higher in the patients whose pleura was opened during surgery as compared to the patients whose pleura was not opened[20]. Rolla et al.[21] emphasized that there was no increase in the incidence of atelectasis or pleural effusion between the 2nd and 5th postoperative day with opening the pleura in the patients who underwent LIMA harvesting. Lim et al.[22], Atay et al.[23], and Oz et al.[16] stated that atelectasis and pleural effusion are significantly more prevalent in the patients, in whom pleura was opened intraoperatively. Atelectasis may be prevalent after CABG due to paralysis/paresis of diaphragm. Fedullo et al. demonstrated left diaphragm dysfunction after CABG in 16% of the patients via US[6]. Application of local cold cardioplegia causes phrenic nerve paresis as well as left inferior lobe atelectasis and increase in effusion between the 2nd and 28th postoperative day[7,8]. In a 30-patient study, Vargas et al.[4] demonstrated 87% atelectasis via computed tomography on the 2nd day after CABG. In the same study, they emphasized that there is significant correlation between the degree of atelectasis and pleural effusion between the 2nd and 7th postoperative day. In our study, we had applied respiratory physiotherapy on all patients from extubation until hospital discharge. There are studies demonstrating that the incidence of pleural effusion is 5-11% in the case of pleura is not opened but increases to 20-50% in the case of pleura is opened during IMA harvesting[9,10]. It has been stated that the incidence of extensive pleural effusion that needs intervention during early postoperative period (first 7 postoperative days) is 0.5-8.5%[3,24,25]. Heidecker et al.[5] reported that the most common causes of pleural effusion in the postoperative early period (first 7 days) are IMA harvesting, diaphragm dysfunction and atelectasis.

CONCLUSIONS In the present study, we compared incidence of pleural effusion in the 7 postoperative days between on-pump CABG and the CABG performed using CPB. Left pleural effusion was encountered to be lower in Group 2 (off-pump). The difference was found to be statistically significant (P<0.05, P=0.006). The conspicuous point is; right, left and bilateral pleural effusion was less prevalent in Group 2 although the number of patients with COPD, which is a factor that enhances atelectasis hence pleural effusion, was higher in Group 2. Under the light of these results, it can be said that left pleural effusion is less prevalent in the patients who underwent offpump CABG as compared to the patients who underwent onpump CABG. We believe that these data should be verified with larger case series. Study limitations In order to create a homogenous group; dialysis patients or the patients with creatinine level higher than 2gr/dl, patients with aortic pathology detected during surgery and thereby surgery procedure was changed, patients who underwent emergency surgery, patients that underwent redo-CABG, patients with postoperative lower respiratory tract infection, patients who developed postoperative diaphragm paralysis, patients who were re-explored because of drainage, and patients who died were not included in the study. Moreover, patients who participate in the study are Caucasians. ACKNOWLEDGMENTS We thank Assoc. Prof. Ismail Keskin (Selçuk University, Zootechnics Division, Department of Biometry and Genetics, Konya, Turkey), PhD for his contributions to the evaluation of results and statistical analysis. Authors’ roles & responsibilities MO FA

Final approval of the manuscript; manuscript writing or critical review of its contents Final approval of the manuscript; manuscript writing or critical review of its contents

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23. Atay Y, Yagdi T, Engin C, Ayik F, Oguz E, Alayunt A, et al. Effect of pleurotomy on blood loss during coronary artery bypass grafting. J Card Surg. 2009;24(2):122-6.

13. Burgess GE 3rd, Cooper JR, Marino RJ, Peuler MJ, Mills NL, Ochsner JL. Pulmonary effect of pleurotomy during and after coronary artery bypass with internal mammary artery versus saphenous vein grafts. J Thorac Cardiovasc Surg. 1978;76(2):230-4.

24. Aarnio P, Kettunen S, Harjula A. Pleural and pulmonary complications after bilateral internal mammary artery grafting. Scand J Thorac Cardiovasc Surg. 1991;25(3):175-8. 25. Light RW, Rogers JT, Cheng D, Rodriguez RM. Large pleural effusions occurring after coronary artery bypass grafting. Cardiovascular Surgery Associates, PC. Ann Intern Med. 1999;130(11):891-6.

14. Berrizbeitia LD, Tessler S, Jacobowitz IJ, Kaplan P, Budzilowicz L, Cunningham JN. Effect of sternotomy and coronary bypass surgery on postoperative pulmonary mechanics. Comparison

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Hermes BM, ORIGINAL et al. - Short-term inspiratory muscle training potentiates the ARTICLE benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program

Short-term inspiratory muscle training potentiates the benefits of aerobic and resistance training in patients undergoing CABG in phase II cardiac rehabilitation program Treinamento muscular inspiratório de curto prazo potencializa os benefícios do treinamento aeróbico e resistido em pacientes após CRM na fase II de programa de reabilitação cardíaca

Bárbara Maria Hermes1, PT; Dannuey Machado Cardoso2, PT, MSc; Tiago José Nardi Gomes3, PT, MSc; Tamires Daros dos Santos1, PT; Marília Severo Vicente1, PT; Sérgio Nunes Pereira4, MD, PhD; Viviane Acunha Barbosa5, PT, PhD; Isabella Martins de Albuquerque5, PT, PhD

DOI: 10.5935/1678-9741.20150043

RBCCV 44205-1666

Abstract Objective: To investigate the efficiency of short-term inspiratory muscle training program associated with combined aerobic and resistance exercise on respiratory muscle strength, functional capacity and quality of life in patients who underwent coronary artery bypass and are in the phase II cardiac rehabilitation program. Methods: A prospective, quasi-experimental study with 24 patients who underwent coronary artery bypass and were randomly assigned to two groups in the Phase II cardiac rehabilitation program: inspiratory muscle training program associated with combined training (aerobic and resistance) group (GCR + IMT, n=12) and combined training with respiratory exercises group (GCR, n=12), over a period of 12 weeks, with two sessions per week. Before and after intervention, the following measurements were obtained: maximal inspiratory and expiratory pressures (PImax and PEmax), peak oxygen consumption (peak VO2) and quality of life scores. Data were compared between

pre- and post-intervention at baseline and the variation between the pre- and post-phase II cardiac rehabilitation program using the Student’s t-test, except the categorical variables, which were compared using the Chi-square test. Values of P<0.05 were considered statistically significant. Results: Compared to GCR, the GCR + IMT group showed larger increments in PImax (P<0.001), PEmax (P<0.001), peak VO2 (P<0.001) and quality of life scores (P<0.001). Conclusion: The present study demonstrated that the addition of inspiratory muscle training, even when applied for a short period, may potentiate the effects of combined aerobic and resistance training, becoming a simple and inexpensive strategy for patients who underwent coronary artery bypass and are in phase II cardiac rehabilitation.

Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil. Department of Physiotherapy. Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS, Brazil. 3 Department of Physiotherapy. Centro Universitário Franciscano (UNIFRA), Santa Maria, RS, Brazil. 4 Cardiac Rehabilitation Program. Hospital Universitário de Santa Maria (HUSM), Santa Maria, RF, Brazil and Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil. 5 Department of Physiotherapy and Rehabilitation. Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.

Financial support: Programa de Auxílio à Pesquisa de Recém-Doutores da Universidade Federal de Santa Maria/Universidade Federal de Santa Maria’s Research Support to Young Researchers Program

Work carried out at the Department of Physiotherapy and Rehabilitation of the Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil.

Article received on March 23rd, 2015 Article accepted on June 21st, 2015

Descriptors: Myocardial Revascularization. Rehabilitation. Exercise. Breathing Exercises.

1 2

Correspondence Address: Isabella Martins de Albuquerque Avenida Roraima, 1000, Cidade Universitária - Bairro Camobi, Santa Maria, RS, Brazil - Zip code: 97105-900 E-mail: albuisa@gmail.com

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combinado (aeróbio e resistido) (GRC + TMI, n=12) e grupo treinamento combinado e exercícios respiratórios (GRC, n=12) durante um período de 12 semanas, com 2 sessões semanais. Antes e após a intervenção, as seguintes mensurações foram obtidas: pressão inspiratória e expiratória máxima (PImáx e PEmáx), consumo de oxigênio de pico (VO2pico) e escore de qualidade de vida. Os dados foram comparados entre o momento pré e pós-intervenção na linha de base e a variação entre o pré e pós-programa de reabilitação cardíaca com uso do teste t de Student, exceto as variáveis categóricas, que foram comparadas pelo teste de qui-quadrado. Foi considerado um P<0,05. Resultados: Comparado ao GRC, o GRC + TMI apresentou maior incremento tanto na PImáx (P<0,001) quanto na PEmáx (P<0,001), no VO2pico (P<0,001) e na qualidade de vida (P<0,001). Conclusão: Demonstrou-se que a adição do programa de treinamento muscular inspiratório, mesmo quando aplicada por um curto período, pode complementar os efeitos do exercício aeróbio combinado ao resistido, tornando-se uma estratégia benéfica para pacientes submetidos à cirurgia de revascularização do miocárdio na Fase II da reabilitação cardíaca.

Abbreviations, acronyms & symbols CABG CAD CRP GCR IMT Peak VO2 PEmax PImax RMS

Coronary artery bypass Coronary artery disease Cardiac rehabilitation program Group of cardiac rehabilitation Inspiratory muscle training Peak oxygen consumption Maximal expiratory pressure Maximal inspiratory pressure Respiratory muscle strength

Resumo Objetivo: Avaliar os efeitos de um programa de treinamento muscular inspiratório em curto prazo associado ao exercício aeróbio e resistido na força muscular respiratória, capacidade funcional e qualidade de vida de pacientes submetidos à cirurgia de revascularização do miocárdio, na Fase II da Reabilitação Cardíaca. Métodos: Trata-se de um estudo quase-experimental, prospectivo, com amostra de 24 pacientes submetidos à cirurgia de revascularização do miocárdio alocados aleatoriamente para Fase II da Reabilitação Cardíaca em dois grupos: grupo de treinamento muscular inspiratório associado ao treinamento

Descritores: Revascularização Miocárdica. Reabilitação. Exercício. Exercícios Respiratórios.

INTRODUCTION

inclusion of resistance training combined with aerobic training for six months during phase II CRP was beneficial to patients with metabolic syndrome submitted to CABG. However, the short-term effects of IMT in patients in phase II CRP after CABG and its association with aerobic and resistance training have been largely unexplored in the literature and require further elucidation. Therefore, the aim of this study was to investigate the efficiency of short-term IMT associated with combined aerobic and resistance training on respiratory muscle strength (RMS), functional capacity, and QoL in patients who underwent CABG and are in phase II CRP.

Cardiovascular diseases are the leading cause of death and disability in Brazil and worldwide. According to the World Health Organization, 7.3 million deaths worldwide were due to coronary artery disease (CAD) in 2008[1]. According to Datasus, in Brazil in 2009 there were 209,029 hospital admissions due to CAD, totaling 12,619 deaths with a mortality rate of 6.04%[2]. Despite advances in clinical therapy and percutaneous interventions, coronary artery bypass grafting (CABG) is still widely used in the treatment of patients with CAD because it can control persistent ischemia and its progression to acute myocardial infarction, as well as provide symptomatic relief and prevent ischemic complications[3]. However, cardiac surgery is a complex procedure that triggers major organ repercussions, which changes the physiology of patients in many ways[4]. In this sense, it has been suggested that respiratory muscle dysfunctions associated with decreased functional capacity contribute to the prolonged period of lung function recovery and the occurrence of physical deconditioning, which can last several weeks in patients submitted to CABG[5,6]. Several studies have demonstrated the effectiveness of inspiratory muscle training (IMT) in restoration of ventilatory function, decrease in the length of hospital stay, and improvement of functional capacity and quality of life (QoL) of patients who underwent CABG and are in phase I cardiac rehabilitation program (CRP)[7-10]. Onishi et al.[11] found that the

METHODS Study design A prospective quasi-experimental study was conducted among patients who underwent CABG and were recruited from the waiting list for a phase II CRP at the Outpatient Cardiology Clinic of Hospital Universitário de Santa Maria (HUSM), Santa Maria, RS, Brazil. The eligibility criteria included patients undergoing CABG up to three weeks before the initiation of the study at HUSM, a clinical course without complications during hospitalization, the absence of smoking (previous or current), and agreement to participate. Patients with chronic obstructive pulmonary disease, unstable angina, acute decompensated heart failure, acute pericarditis or myocarditis, complex arrhythmias, uncontrolled hypertension, severe orthopedic or neurological disorders, uncontrolled diabetes, and labyrinthitis were excluded.

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The study was approved by the Research Ethics Committee of Universidade Federal de Santa Maria (UFSM) under protocol no. 16149813.3.0000.5346 and was conducted in accordance with the Guidelines and Norms Regulating Research Involving Humans established by Resolution no. 466/2012 of the National Health Council.

Inspiratory Muscle Training The participants assigned to the GCR+IMT group were subjected to IMT, using the IMT Threshold® equipment (Threshold Inspiratory Muscle Trainer, Health Scan Products Inc., Cedar Grove, NJ, USA) in 3 sets of 10 repetitions with an inspiratory load of 30% of the maximal inspiratory pressure (PImax)[13]. During training, the participants remained seated with the nose occluded by a nose clip and were advised to maintain a diaphragmatic breathing pattern and a respiratory rate between 15 and 20 cycles per minute. Each week, the training load was adjusted to maintain 30% of the PImax.

Patients and Intervention Patients eligible for the study were initially assessed via anamnesis, physical examination, and evaluation of inspiratory muscle strength. Subsequently, these patients were randomly allocated to phase II of the CRP into two groups: a group subjected to CRP+IMT (GCR+IMT) followed the IMT protocol in addition to the combined training (aerobic and resistance training) and a group subjected to CRP (GCR) followed the combined training protocol and performed breathing exercises for 12 weeks. An RMS test was conducted before and after the intervention, and the functional capacity and QoL were evaluated. All evaluations were conducted by investigators blinded to the allocation of patients into the intervention groups.

Assessment of Respiratory Muscle Strength PImax and maximal expiratory pressure (PEmax) were measured using a digital manometer (MVD-300, Globalmed, Porto Alegre, RS, Brazil)[14]. A 2-mm orifice in the system kept the glottis open and prevented any interference from pressure produced by facial muscles. First, the subjects were instructed to remain in a seated position. A demonstration of how the maneuvers should be carried out was given and then performed by the subject after the placement of a nose clip. The subjects were instructed to keep their lips sealed tightly around the mouthpiece so no air could escape. PImax values were obtained by inspiration from residual volume[14], which was repeated at least three times with a one-minute interval between repetitions. PEmax was obtained by expiration from total lung capacity, using the same methodology applied in inspiration. During the PImax maneuver, the subject kept the mouthpiece in the oral cavity only during the inspiration, and in the PEmax maneuver, only during expiration. The maneuvers were sustained at maximal force for approximately one second and the highest value was computed from a minimum of three repetitions for each maneuver, with a maximum difference of 10% between values and they were then compared to the predicted values a​ ccording to the equations proposed by Neder et al.[15].

Cardiac Rehabilitation Program All patients participated in the CRP for a period of 12 weeks, with two sessions per week (24 sessions). Each session lasted 60 minutes, and all sessions were under the direct supervision of a physical therapist. The training program consisted of a combination of aerobic and resistance exercises, 30 minutes of aerobic exercise on a treadmill and exercise bike, 20 minutes of resistance exercises for the arms (latissimus dorsal m.,biceps brachii m., triceps brachii m., deltoid m., trapezius m., pectoralis major m., pectoralis major m., and rhomboid m) and legs (femoral quadriceps m., hip adductors m. and hip abductors m.) with dumbbells, ankle weights, or elastic bands (3 sets of exercises for each muscle group performed with 10 repetitions with the intensity adjusted to 50% of the load of one maximum repetition - 1MR), and 10 minutes of stretching and relaxation. Heart rate, blood pressure, and peripheral oxygen saturation were measured at the beginning, during, immediately after, and five minutes after each session. The exercise intensity was based on the percentage of heart rate reserve, calculated as the difference between the maximum heart rate obtained in the exercise stress test and the resting heart rate, with the establishment of an intensity of 55%–65%[12] and a score of 4-6 on the modified Borg scale (ranging between 0 and 10). In addition to the CRP, the participants performed diaphragmatic stimulation and fractionated breathing patterns (short inspirations during three intervals with a mild inspiratory pause) to achieve a diaphragmatic breathing pattern similar to that performed by the GCR+IMT.

Assessment of Functional Capacity Functional capacity was evaluated by exercise testing (ET) using a standard Bruce protocol and assessed with peak oxygen consumption (peak VO2). The values of peak VO2 were obtained by use of a treadmill stress test (Imbramed® KT 10200, Sao Paulo, Brazil), and the analysis of peak VO2 was carried out using the Ergo PC version 2.2 (MicromedTM, Brazil) software. The ET was performed according to the guidelines of the Brazilian Society of Cardiology/Department of Exercise, Ergometry, and Cardiovascular Rehabilitation[16]. Evaluation of Quality of Life QoL was assessed with the Portuguese version of the Minnesota Living with Heart Failure Questionnaire (MLwHFQ)[17]. Sample size calculation To estimate the sample size, a pilot study was conducted

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using a protocol identical to that described above in a group of five patients. A sampling error of 2%, a two-sided alpha of 5%, a statistical power of 80%, and a difference of 20.6±9.6 cmH2O in variation of PImax between the groups were considered as well as a 10% loss to follow-up, thus resulting in the inclusion of at least nine patients per group.

values between groups were compared using the independent Student’s t-test, except for the categorical variables, which were compared by the Chi-square test. A value of P<0.05 was considered statistically significant.

Statistical Analysis Data were analyzed using the statistical software SPSS version 20.0. The normality of the variables was assessed with the Shapiro-Wilk test. Categorical data are presented as absolute frequencies and percentages. Continuous data with normal distribution are expressed as means and standard deviations. Student’s t-test for paired samples was used to compare the data before and after the intervention. The baseline data and the variation between pre- and post-CRP

Of the 28 eligible patients, four were excluded for not meeting the inclusion criteria. Therefore, 24 patients were included in the study. Of these, 12 patients were allocated to the GCR and 12 were allocated to the GCR+IMT. No adverse events were observed during the CRP and adherence to the program was considered excellent. The demographic, anthropometric, and clinical characteristics of both groups are shown in Table 1. No significant differences were observed between the two groups.

RESULTS

Table 1. Demographic and clinical characteristics of patients participating in the study. Baseline characteristics GCR (n=12) GCR+IMT (n=12) P Age (years) 59.5±8.7 55.2±7.9 0.313 Male gender, n (%) 10 (83.3) 7 (58.3) 0.178 BMI (Kg/m2) 28.4±3.8 30.7±4.4 0.274 Diabetes, n (%) 4 (33.33) 3 (25.0) 0.500 Hypertension, n (%) 4 (33.33) 5 (41.6) 0.312 Ejection fraction (%) 65.2±9.9 63.5±3.6 0.640 NYHA I, n (%) 2 (16.7) 3 (25.0) 0.849 II, n (%) 8 (66.7) 6 (50.0) 0.408 III, n (%) 2 (16.7) 3 (25.0) 0.849 Extent of disease (%) 2-vessel 54.3 50.5 0.285 3-vessel 45.7 49.5 Extracorporeal circulation, n (%) 12 (100) 12 (100) Duration of hospitalization after surgery (days) 6.7±1.7 7.1±1.5 0.657 Peak VO2 (mL.Kg1.min-1) 26.0±5.6 25.5±3.7 0.802 Peak VO2 (% predicted) 88.1±23.0 86.4±16.0 0.836 PImax (cmH2O) 72.0±8.1 67.8±9.0 0.782 PImax (% predicted) 71.4±13.8 70.4±11.1 0.856 PEmax (cmH2O) 87.3±11.0 86.6±25.9 0.936 PEmax (% predicted) 80.2±13.9 86.1±27.7 0.518 MLwHFQ (score) 39.9±12.6 41.0±19.0 0.871 Medication, n (%) Acetylsalicylic acid 8 (66.6) 6 (50.0) 0.408 Clopidogrel or triclopidine 2 (16.7) 1 (8.3) 0.500 Statin 6 (50.0) 6 (50.0) 1.000 Diuretics 4 (33.3) 3 (25.0) 0.500 Warfarin 1 (8.3) 2 (16.7) 0.500 ACEI or ARB 4 (33.3) 5 (41.6) 0.500 Beta-blockers 8 (66.6) 9 (75.0) 1.000 Data are expressed as mean ± standard deviation or absolute values and percentages. ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; BMI=body mass index; GCR=cardiac rehabilitation group; GCR+IMT=cardiac rehabilitation group + inspiratory muscle training program; MLwHFQ=Minnesota living with heart failure questionnaire; NYHA=New York Heart Association; Peak VO2=peak oxygen consumption; PEmax=maximal expiratory pressure; PImax=maximal inspiratory pressure

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A significant increase in PImax and PEmax was observed after CRP in both groups. However, the variation between pre- and post-CRP values was significantly higher in the GCR+IMT (Table 2). Regarding functional capacity, it was observed that in the pre-CRP phase, the GCR group achieved approximately 88% of predicted peak VO2 whereas patients in the GCR+IMT achieved approximately 86% (Table 1). After intervention, patients in the GCR + IMT improved significantly their peak VO2. Additionally, the variation of peak VO2 was significantly higher in the GCR+TMI compared to the GCR, and a similar result was demonstrated for the percent-predicted peak VO2 (% predicted peak VO2) (Figures 1 and 2). The total MLwHFQ scores decreased significantly in both groups, indicating improvement in QoL, however, the variation in MLwHFQ scores was significantly higher in the GCR + IMT (Figure 3).

DISCUSSION The present study found that a short-term IMT program associated with combined aerobic and resistance training had a more pronounced effect on respiratory muscle strength, functional capacity and QoL than combined aerobic and resistance training alone in patients who underwent CABG surgery and are in phase II CRP. To the best of our knowledge, this is the first study to address the additional short-term effects of IMT associated with combined training in this patient population. Despite the current lack of evidence demonstrating the benefits of IMT in patients who underwent CABG surgery and are in phase II CRP, it is important to mention the pioneering study of Winkelmann et al.[18], which also investigated the potential additional benefits of IMT combined with aerobic training for 12 weeks, although in a different population (patients with chronic heart failure – CHF). Their

Table 2. Comparison of respiratory muscle strength between groups. Variables GCR (n=12) Pre Post Variation P* 87.3±11.0 89.8±10.5 2.3±0.8 0.004 PEmax (cmH2O) 80.2±13.9 82.2±15.6 2.5±0.8 0.038 PEmax (% predicted) 72.0±8.3 77.0±5.8 4.9±0.2 <0.001 PImax (cmH2O) 71.4±13.8 76.4±12.8 4.7±0.9 <0.001 PImax (% predicted)

GCR+IMT (n=12) Pre Post Variation 86.6±25.9 108.1 ±17.1 21.5±8.5 86.1±27.7 108.1±21.1 22.0±7.7 67.8±9.0 96.7±21.3 28.9±7.9 70.4±11.1 99.6±16.7 29.1±5.6

P* <0.001 <0.001 <0.001 <0.001

P** <0.001 <0.001 <0.001 <0.001

Data are expressed as mean ± standard deviation. GCR=cardiac rehabilitation group; GCR+IMT=cardiac rehabilitation group + inspiratory muscle training program; PEmax=maximal expiratory pressure; Pimax=maximal inspiratory pressure *P-value derived using paired Student’s t-test, after checking for normal distributions. **P-value derived using independent Student’s t-test for comparison of variation between the groups.

Fig. 1 - Comparison of peak oxygen consumption (peak VO2 ) between groups.

Fig. 2 - Comparison of peak oxygen consumption (% predicted) between groups.

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Regarding QoL, the values of MLwHFQ scores improved significantly in both groups. However, the IMT group showed a higher variation in MLwFQ scores. These changes may explain the additional improvement in QoL with IMT associated with combined training. Few studies have evaluated the impact of IMT associated with aerobic and resistance training on QoL specifically in patients who underwent CABG and are in phase II CRP. The addition of IMT to training programs is becoming more widespread as a potential non-pharmacological therapeutic intervention to improve QoL of patients with CHF[18,19]. Recently, Adamopoulos et al.[24], in a 12-week prospective randomized multicenter study, have reported that IMT associated with aerobic training improves QoL in patients with CHF. We consider that our results are relevant because even a short-term IMT program performed just twice a week with a lower inspiratory resistive loading intensity improved the variables analyzed, although it was carried out in patients without respiratory muscle weakness. Furthermore, these findings are consistent with results of previous studies conducted with patients with CHF subjected to the IMT program, though performed at higher weekly frequency and with a higher inspiratory loading intensity training protocol. Some study limitations should be considered. First, our sample included only 24 patients submitted to CABG. However, it is of note that the number of patients who participate in phase II CRP in Brazil is extremely low. Second, an inspiratory muscle endurance testing was not performed. The third limitation is related to learning the technique of assessment of respiratory muscle strength. This test depends on the understanding and cooperation of participating individuals. Therefore, the technique can have a determinative positive effect on the outcome. This aspect can be considered as qualitatively influencing the results of the present study.

Fig. 3 - Comparison of change in QoL score, assessed with Minnesota Living with Heart Failure questionnaire (MLwHFQ), between groups.

study demonstrated that the addition of IMT to aerobic exercise resulted in additional improvement in PImax compared to aerobic exercise alone, and these results were similar to those reported in this study. Recently, Laoutaris et al.[19], using a protocol similar to ours, showed that IMT associated with combined aerobic and resistance training in 27 patients with CHF, without inspiratory muscle weakness, is safe, and resulted in incremental benefits in PImax compared with the effects of aerobic training alone. Studies have been conducted to evaluated the effects of combined aerobic and resistance training on functional capacity of patients undergoing CABG. Onishi et al.[11] and Sumide et al.[20] showed that combined training induced significant improvement in peak VO2 in this patient population. In contrast, Arthur et al.[21], in a randomized controlled trial to compare the effect of 6 months of combined aerobic and resistance training vs aerobic training alone in women undergoing CABG, reported that after the exercise training program both groups showed statistically significant improvements in peak VO2. In the present study, even over a relatively short-term period, it was observed that IMT associated with combined aerobic and resistance training provides a significant improvement in functional capacity when compared to combined training. These results indicate that the addition of IMT may have complementary effects to those obtained with combined training on functional capacity of patients who underwent CABG and are in phase II CRP. One potential explanation of this finding is that the IMT program, even over a shortterm period, improves systemic vasodilation and perfusion of peripheral muscles[22], promoting a more pronounced effect on functional capacity in these patients. Laoutaris et al.[23] showed that addition of IMT program to aerobic training in patients with ventricular assist device resulted in an additional improvement in peak VO2, compared with the effects of aerobic training alone.

CONCLUSION This study demonstrates that a short-term IMT program associated with aerobic and resistance training in patients undergoing phase II of a CRP after CABG resulted in significantly large increments in respiratory muscle strength, functional capacity, and QoL. Our single-center findings also indicate that the addition of IMT, even when applied for a short period, can complement and enhance the effects of combined aerobic and resistance training and could become a simple and inexpensive adjuvant treatment, improving the efficiency of phase II cardiac rehabilitation programs within the public health system. Future large multicenter studies are needed to provide definitive proof of these benefits. Source of funding This study was financially supported by the Research Funding Program (FIPE)/UFSM.

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8. Savci S, Degirmenci B, Saglam M, Arikan H, Inal-Ince D, Turan HN, et al. Short-term effects of inspiratory muscle training in coronary artery bypass graft surgery: a randomized controlled trial. Scand Cardiovasc J. 2011;45(5):286-93.

Authors’ roles & responsibilities BMH

DMC TJNG TDS MSV SNP VAB IMA

Analysis and/or interpretation of data; final approval of the manuscript; study design; implementation of projects and/ or experiments; manuscript writing or critical review of its content Analysis and/or interpretation of data; statistical analysis; final approval of the manuscript; manuscript writing or critical review of its content Final approval of the manuscript; study design; implementation of projects and/or experiments; manuscript writing or critical review of its content Final approval of the manuscript; implementation of projects and/or experiments; manuscript writing or critical review of its content Final approval of the manuscript; implementation of projects and/or experiments; manuscript writing or critical review of its content Final approval of the manuscript; study design; manuscript writing or critical review of its content Final approval of the manuscript; study design; manuscript writing or critical review of its content Analysis and/or interpretation of data; Statistical analysis; final approval of the manuscript; study design; manuscript writing or critical review of its content

9. Ferreira PEG, Rodrigues AJ, Évora PRB. Efeitos de um programa de reabilitação da musculatura inspiratória no pós-operatório de cirurgia cardíaca. Arq Bras Cardiol. 2009;92(4):275-82. 10. Matheus GB, Dragosavac D, Trevisan P, Costa CE, Lopes MM, Ribeiro GC. Inspiratory muscle training improves tidal volume and vital capacity after CABG surgery. Rev Bras Cir Cardiovasc. 2012;27(3):362-9. 11. Onishi T, Shimada K, Sunayama S, Ohmura H, Sumide T, Masaki Y, et al. Effects of cardiac rehabilitation in patients with metabolic syndrome after coronary artery bypass grafting. J Cardiol. 2009;53(3):381-7. 12. Mahler DA; American College of Sports Medicine. ACSM’s guidelines for exercise testing and prescription, 5th ed. Baltimore: Williams & Wilkins; 1995.

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18. Winkelmann ER, Chiappa GR, Lima CO, Viecili PR, Stein R, Ribeiro JP. Addition of inspiratory muscle training to aerobic training improves cardiorespiratory responses to exercise in patients with heart failure and inspiratory muscle weakness. Am Heart J. 2009;158(5):768.e1-7.

6. Ades PA, Savage PD, Brawner CA, Lyon CE, Ehrman JK, Bunn JY, et al. Aerobic capacity in patients entering cardiac rehabilitation. Circulation. 2006;113(23):2706-12.

19. Laoutaris ID, Adamopoulos S, Manginas A, Panagiotakos DB, Kallistratos MS, Doulaptsis C, et al. Benefits of combined aerobic/resistance/inspiratory training in patients with chronic heart failure. A complete exercise model? A prospective randomised study. Int J Cardiol. 2013;167(5):1967-72.

7. Barros GF, Santos CS, Granado FB, Costa PT, Límaco RP, Gardenghi G. Respiratory muscle training in patients submitted to coronary arterial bypass graft. Rev Bras Cir Cardiovasc. 2010;25(4):483-9.

20. Sumide T, Shimada K, Ohmura H, Onishi T, Kawakami K, Masaki Y, et al. Relationship between exercise tolerance and muscle

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strength following cardiac rehabilitation: comparison of patients after cardiac surgery and patients with myocardial infarction. J Cardiol. 2009;54(2):273-81.

23. Laoutaris ID, Dritsas A, Adamopoulos S, Manginas A, Gouziouta A, Kallistratos MS, et al. Benefits of physical training on exercise capacity, inspiratory muscle function, and quality of life in patients with ventricular assist devices long-term postimplantation. Eur J Cardiovasc Prev Rehabil. 2011;18(1):33-40.

21. Arthur HM, Gunn E, Thorpe KE, Ginis KM, Mataseje L, McCartney N, et al. Effect of aerobic vs combined aerobicstrength training on 1-year, post-cardiac rehabilitation outcomes in women after a cardiac event. J Rehabil Med. 2007;39(9):730-5.

24. Adamopoulos S, Schmid J, Dendale P, Poerschke D, Hansen D, Dritsas A, et al. Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure: The Vent-HeFT trial: a European prospective multicentre randomized trial. Eur J Heart Fail. 2014;16(5):574-82.

22. Chiappa GR, Roseguini BT, Vieira PJ, Alves CN, Tavares A, Winkelmann ER, et al. Inspiratory muscle training improves blood flow to resting and exercising limbs in patients with chronic heart failure. J Am Coll Cardiol. 2008;51(17):1663-71.

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Hossne JuniorORIGINAL NA, et al. -ARTICLE Cardiopulmonary bypass increases the risk of vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure

Cardiopulmonary bypass increases the risk of vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure O uso da circulação extracorpórea aumenta o risco de síndrome vasoplégica em pacientes com insuficiência renal crônica hemodialítica submetidos à revascularização cirúrgica do miocárdio

Nelson Américo Hossne Junior1, MD, PhD; Matheus Miranda1; Marcus Rodrigo Monteiro1; João Nelson Rodrigues Branco1, MD, PhD; Guilherme Flora Vargas1, MD, PhD; José Osmar Medina de Abreu Pestana1, MD, PhD; Walter José Gomes1, MD, PhD

DOI: 10.5935/1678-9741.20140092

RBCCV 44205-1667

Abstract Objective: Coronary artery bypass grafting is currently the best treatment for dialysis patients with multivessel coronary artery involvement. Vasoplegic syndrome of inflammatory etiology constitutes an important postoperative complication, with highly negative impact on prognosis. Considering that these patients have an intrinsic inflammatory response exacerbation, our goal was to evaluate the incidence and mortality of vasoplegic syndrome after myocardial revascularization in this group. Methods: A retrospective, single-center study of 50 consecutive and non-selected dialysis patients who underwent myocardial revascularization in a tertiary university hospital, from 2007 to 2012. The patients were divided into 2 groups, according to the use of cardiopulmonary bypass or not (off-pump coronary artery bypass). The incidence and mortality of vasoplegic syndrome were analyzed. The subgroup of vasoplegic patients was studied separately. Results: There were no preoperative demographic differences

between the cardiopulmonary bypass (n=20) and off-pump coronary artery bypass (n=30) group. Intraoperative data showed a greater number of distal coronary arteries anastomosis (2.8 vs. 1.8, P<0.0001) and higher transfusion rates (65% vs. 23%, P=0.008) in the cardiopulmonary bypass group. Vasoplegia incidence was statistically higher (P=0.0124) in the cardiopulmonary bypass group (30%) compared to the off-pump coronary artery bypass group (3%). Vasoplegia mortality was 50% in the cardiopulmonary bypass group and 0% in the off-pump coronary artery bypass group. The vasoplegic subgroup analysis showed no statistically significant clinical differences. Conclusion: Cardiopulmonary bypass increased the risk for developing postoperative vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure.

Escola Paulista de Medicina da Universidade Federal de São Paulo (EPMUNIFESP), São Paulo, SP, Brazil.

Correspondence Address: Nelson Américo Hossne Junior Rua Napoleão de Barros, 715, 3º andar - Vila Clementino São Paulo, SP, Brazil - Zip code: 04024-002 E-mail: nelson.hossne@gmail.com

Descriptors: Myocardial Revascularization. Renal Insufficiency, Chronic. Vasoplegic Syndrome. Cardiopulmonary Bypass.

1

This study was carried out in the Cardiovascular Surgery Course of the Surgery Department of Escola Paulista de Medicina at Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil.

Article received on February 25th, 2014 Article accepted on July 7th, 2014

No financial support.

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revascularização miocárdica, em um hospital terciário universitário, no período de 2007 a 2012. Esses pacientes foram divididos em 2 grupos, de acordo com o emprego ou não da circulação extracorpórea. A incidência e a mortalidade da vasoplegia foram analisadas nos grupos. Após a identificação dos pacientes quanto à presença de vasoplegia, este subgrupo foi estudado separadamente. Resultados: Não houve diferenças demográficas pré-operatórias entre os grupos com circulação extracorpórea (n=20) e sem circulação extracorpórea (n=30). Dados intraoperatórios demonstraram maior número de artérias coronárias revascularizadas (2,8 vs. 1,8; P<0,0001) e maior necessidade de transfusão (65% vs. 23%; P=0,008) no grupo circulação extracorpórea. A incidência de vasoplegia foi estatisticamente maior (P=0,0124) no grupo circulação extracorpórea (30%) em comparação ao grupo sem circulação extracorpórea (3%). A mortalidade dos pacientes com vasoplegia foi 50% no grupo circulação extracorpórea e 0% no grupo sem circulação extracorpórea. A análise do subgrupo vasoplégico não demonstrou diferenças clínicas estatisticamente significantes. Conclusão: O emprego da circulação extracorpórea na revascularização cirúrgica do miocárdio em pacientes com insuficiência renal crônica dialítica aumentou o risco para desenvolvimento de síndrome vasoplégica pós-operatória.

Abbreviations, acronyms & symbols ACE ACT CABG CI COPD CPB CRF LV MAP OPCAB SVRI

Angiotensin-converting enzyme Activated clotting time Coronary artery bypass grafting Cardiac index Chronic obstructive pulmonary disease Cardiopulmonary bypass Chronic renal failure Left ventricle Mean arterial pressure Off-pump coronary artery bypass. Systemic vascular resistance index

Resumo Objetivo: O melhor tratamento atual para os pacientes dialíticos com acometimento coronariano multiarterial é a revascularização cirúrgica do miocárdio. Dentre as complicações pós-operatórias, a síndrome vasoplégica de etiopatogenia inflamatória torna-se importante pelo impacto altamente negativo no prognóstico. Considerando que esses pacientes possuem uma exacerbação intrínseca da resposta inflamatória, nosso objetivo foi avaliar a incidência e a mortalidade da síndrome vasoplégica no pós-operatório de revascularização miocárdica nesse grupo. Métodos: Estudo retrospectivo, unicêntrico, de 50 pacientes dialíticos consecutivos e não selecionados, submetidos à

Descritores: Revascularização miocárdica. Insuficiência Renal Crônica. Vasoplegia. Circulação Extracorpórea.

INTRODUCTION

International guidelines recommend performing coronary artery bypass surgery without the use of CPB in dialysis patients, whenever possible, since its use can lead to increased postoperative morbidity[7,8]. Vasoplegic syndrome is a well-recognized complication in the postoperative setting of cardiovascular surgery, initially described by Gomes et al.[9,10]. It can be defined as a hemodynamic shock, resembling septic shock syndrome, in which there is evidence of decreased systemic vascular resistance index, increased cardiac index and severe hypotension with the use of vasoactive drugs, initiating in the early postoperative hours. Although the mechanisms are not fully understood, most authors propose a direct correlation between the release of inflammatory mediators and severe vasodilation with consequent vasoplegic syndrome[11-13]. Its incidence varies widely among several reports, between 5% and 44%, with median values of 10%. Higher incidence values are generally found in groups considered at high risk of developing vasoplegia, such as patients with left ventricular assistance, ventricular dysfunction, preoperative use of angiotensin converting enzyme inhibitors and heparin, and other factors with discordant correlation reported[11,14-16]. Considering the well-established inflammatory pathogenesis of coronary atherosclerosis, the inherent chronic inflammatory status presented in patients with CRF requiring dialysis[17], the greater inflammatory response in patients un-

Chronic renal failure (CRF) constitutes an independent risk factor for chronic coronary artery disease, and the severity of coronary lesions are inversely proportional to glomerular filtration rate[1]. Several patients’ characteristics are associated with a greater severity of coronary disease in this group, such as uremia, poor quality of distal coronary bed, hyperhomocysteinemia, increased calcium-phosphorus product, oxidative stress, among others. Additionally, the chronic inflammatory status enhanced by CRF contributes to amplify the already established inflammatory pathogenesis of coronary atherosclerosis[2]. Thus, ischemic cardiovascular diseases are the leading cause of mortality in this class of patients[1]. Coronary artery bypass grafting (CABG) shows greater long-term survival and lower risk of myocardial infarction and death from cardiovascular events compared to coronary angioplasty and stenting in patients with chronic renal failure requiring dialysis therapy[3]. However, this group of patients experiences high morbidity and mortality mainly due to the presence of multiple preoperative comorbidities[4]. Furthermore, several reports have shown greater inflammatory response in patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB) compared to off-pump surgery[5,6].

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dergoing CPB, as well as the inflammatory mediators intrinsically linked to severe vasodilation of the vasoplegic syndrome, we would expect a higher incidence of vasoplegia in dialysis patients undergoing CABG with CPB. Therefore, our objective was to analyze the incidence and mortality of vasoplegic syndrome in patients with CRF/dialysis who underwent CABG with and without the use of CPB.

carefully, avoiding the left pleura space opening. The saphenous vein was removed through small incisions on the thigh. The use of cardiopulmonary bypass or off-pump technique was based on the main surgeon judgment criteria, according to each patient characteristics. Technique with cardiopulmonary bypass CPB establishment (Braile Biomédica, Sao José do Rio Preto, São Paulo, Brazil), including arterial and venous cannulas, consisted of a standard circuit with cardiotomy reservoir, membrane oxygenator, roller pump, and arterial line filter. Heparin (Blausiegel, Blau, São Paulo, Brazil) was administered before aortic and atrial cannulation (dual-stage cannula) at a dose of 4 mg/kg, directly in the right atrium. Cardiopulmonary bypass with mild systemic hypothermia (32° C), at a rate of 1.8 L/m2/ min to maintain MAP>60 mmHg, was initiated only after activated coagulation time (ACT) (MCA-2000, Adib Jatene Foundation, São Paulo, Brazil) above 480 seconds, ten minutes after heparin administration. Noradrenaline was administered for patients with MAP < 60 mmHg during CPB, despite adequate blood volume and flow. Heparin dosage and efficacy during CPB was controlled by sequential ACT measurements, every 30 minutes, and supplemented with 1 mg/kg heparin whenever ACT < 480 seconds. Myocardial protection with anterograde hypothermic (4°C) blood cardioplegia (25% hematocrit) was intermittently performed every 15 minutes through aortic puncture, with 400 mL/min flow (MAP > 60 mmHg), and pulmonary artery trunk continuous aspiration (left ventricle drainage) during cardiac arrest with continuous aortic cross clamping.

METHODS This was a single-center, retrospective study of 50 consecutive patients with chronic renal failure on dialysis referred for CABG at a tertiary public university hospital, from 2007 to 2012. Patients with concomitant surgical procedures (valve surgery, carotid, aortic, etc.) were excluded from the study. Patients` demographic and clinical characteristics, intraoperative data and postoperative complications during hospitalization were evaluated, as well as the incidence and mortality of postoperative vasoplegic syndrome. Vasoplegic syndrome was defined by hypotension (MAP<60 mmHg) refractory to vasopressor drugs administration (norepinephrine, epinephrine and vasopressin), decreased systemic vascular resistance index (SVRI<1.600 dyn∙sec/cm5/m2) and high cardiac index (CI>2.5 L/min/m2), measured by continuous thermodilution catheter. The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) was used for preoperative risk calculation[18]. Patient sample was divided into two groups, according to the use of CPB, in order to identify variables that implied higher morbidity and in-hospital mortality, with detailed specific analysis in the subgroup of patients with vasoplegia. The study was approved by the Institutional Ethics Committee.

Off-Pump Technique Heparin (Blausiegel, Blau, São Paulo, Brazil) was administered 10 minutes prior to coronary occlusion at a 2 mg/kg dose. Distal anastomoses were performed employing a suction stabilizer (Octopus, Medtronic, Inc., Minneapolis, MN, United States), with only proximal tourniquet of coronary arteries with Polypropylene 5-0 (Prolene, Johnson & Johnson, New Jersey, NY, United States). Coronary anastomoses of totally occluded vessels were prioritized. Heparin reversal was performed at the end of the surgery for all patients, with protamine at a 1:1 dose, through a peripheral intravenous route, regardless of the surgical technique.

Surgical technique for coronary artery bypass grafting Surgical referral for myocardial revascularization was based on American and European guidelines[15,16], with all patients with class I recommendation – obstructive lesions greater than 50% in the left main coronary or greater than 70% in patients with multivessel and proximal left anterior descending disease. All patients underwent hemodialysis with heparin and subsequent reversal with protamine the day before the surgical procedure. Preoperative planning was done according to the severity of the coronary lesions and possibility of surgical revascularization of the distal coronary bed. Surgical technique was standardized with the left internal thoracic artery for revascularization of the anterior descending artery, and saphenous vein used for other coronary beds, with proximal anastomosis in the ascending aorta. All patients were operated through median sternotomy. Dissection of the left internal thoracic artery was performed very

Statistical analysis Chi-square and Fisher exact tests were used for qualitative variables to compare the groups according to the use of CPB. Mann-Whitney test was employed for quantitative variables. These same tests were also used for comparison between subsets of vasoplegic patients. Statistical significance was set at 0.05 or 5%. Statistical tests were calculated with the BioEstat 5.0 software.

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RESULTS

patients, according to the use of cardiopulmonary bypass, is described in Table 4. The mean ± standard deviation of bypass and aortic cross clamp times in the CPB patients who developed vasoplegia compared to patients who did not develop vasoplegia in the same group are shown in Table 5. Vasoplegic syndrome mortality was 50% (3/6) in the CPB subgroup. There were no deaths in the off-pump group (0/1).

Demographic data of all patients are shown in Table 1. Sixteen percent of patients had left main coronary artery lesions (greater than 50% obstruction). The remaining patients (84%) had multivessel disease. Three patients were in immunosuppressive therapy due to prior renal transplant; however, they returned to dialysis therapy after kidney graft rejection. No patients had preoperative hemodynamic instability nor were they referred for urgent or emergency surgery. Intraoperative variables are presented in Table 2. There were no intraoperative deaths. Vasoplegic syndrome incidence was 30% in the CPB group and 3% in the off-pump group, as shown in Table 3. The analysis of clinical characteristics of the vasoplegic

DISCUSSION The high prevalence of cardiovascular risk factors in patients with chronic renal failure in dialysis therapy in this study reiterates ischemic cardiovascular disease as the leading cause of mortality in this group of patients.

Table 1. Demographic characteristics, according to the use of cardiopulmonary bypass. Demographic Characteristics CPB n 20 Age (years) 57.1 Female gender (%) 20 Dialysis time (months) 3.5 Hypertension (%) 100 Diabetes (%) 70 Dyslipidemia (%) 50 Obesity (%) 5 Smoking (%) 15 COPD (%) 0 Previous stroke (%) 15 Previous coronary stenting (%) 25 Previous cardiac surgery (%) 0 Congestive heart failure (%) 25 Previous myocardial infarction (%) 15 Peripheral artery disease (%) 15 Stable angina (%) 10 Unstable angina (%) 15 Left main disease (%) 15 LV ejection fraction > 50% 80 EuroSCORE II 2.5

Off-pump 30 56.1 37 5.0 100 72.6 37 20 7 0 17 27 0 23 20 20 17 13 17 77 2.8

Table 2. Intraoperative variables, according to the use of cardiopulmonary bypass.

P value 0.68 0.96 0.34 0.68 1.00 0.95 0.52 0.22 0.38 1.00 1.00 0.84 1.00 0.81 0.72 0.72 0.69 0.99 1.00 1.00 0.83

Intraoperative variable Number of coronary anastomosis Inotropic support (%) Blood transfusion (%)

CPB 2.8 85 65

P value <0.0001 1.00 0.008

Table 3. Incidence of postoperative vasoplegia, according to the use cardiopulmonary bypass. Vasoplegia Incidence (%)

CPB 30

Off-pump 3

P value 0.01

Table 4. Vasoplegic subgroup characteristics, according to the use of cardiopulmonary bypass. Vasoplegic subgroup n AAS Preoperative Beta-blocker medication ACE inhibitor Statin LV ejection fraction > 50% Diabetes (%)

COPD=chronic obstructive pulmonary disease; CPB=cardiopulmonary bypass; LV=left ventricle; Left main disease=obstructive lesion greater than 50%

CPB 6 100% 83.3% 16.7% 100% 100% 66.7%

Table 5. Average ± standard deviation (in minutes) of bypass and aortic cross clamp times, according to the development of postoperative vasoplegia. Mean time ± standard deviation Bypass Aortic cross clamp

Off-pump 1.8 40 23

Vasoplegia 102.7±20.5 58.5±16.6

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P value 0.08 0.90

Off-pump 1 100% 100% 0% 100% 100% 100%

P value 0.01 1.00 1.00 1.00 1.00 1.00 1.00


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Considering our consecutive series, 52% of patients had no cardiovascular symptoms, and 92% presented with preserved left ventricular function. It is noteworthy that most patients were referred for CABG after the diagnosis of severe coronary lesions in elective coronary angiography protocol for kidney pre-transplant evaluation; particularly, if we consider that CABG reduces kidney transplant operative risk, and increases the immediate survival of these patients[19]. Group pairing comparison, according to the use of CPB, demonstrated no statistical differences in relation to preoperative demographic data or surgical risk, even in a retrospective analysis. Intraoperative data showed a higher mean number of distal anastomosis in the CPB group compared to the off-pump group. The bad quality of the thin distal coronary bed in some patients precluded a complete revascularization, despite the typical multivessel involvement usually present in dialysis patients. The criteria on whether to use CPB were homogeneous since the same surgical team performed all surgeries. It is important to point out that the diagnosis of vasoplegic syndrome was conducted in an objective manner, with assessment of all hemodynamic measurements through continuous thermodilution catheter, defined by hypotension (MAP<60 mmHg) refractory to vasopressor drugs administration (norepinephrine, epinephrine and vasopressin), decreased systemic vascular resistance index (SVRI<1.600 dyn∙sec/cm5/m2), and high cardiac index (CI > 2.5 L/min/m2). Overall incidence of vasoplegia in our study was 12%. However, a higher incidence (P=0.01) of vasoplegic syndrome was observed in patients with chronic renal failure/ dialysis who underwent on-pump CABG surgery (30%) compared to the off-pump group (3%). Analysis of the vasoplegic subgroup did not show any statistically significant differences in relation to clinical characteristics, according to the use of CPB. Published data had shown that preoperative use of ACE inhibitors has been associated with an increased risk of vasoplegic syndrome[16]. Nevertheless, no differences were detected in the use of preoperative medications, including ACE inhibitors, beta blockers, aspirin or statins in the vasoplegic subgroup. Cardiopulmonary bypass time in patients who developed vasoplegia was slightly higher than in patients without vasoplegic syndrome, within the CPB group (P=0.08). However, evidence supports a direct correlation between longer CPB times and the risk of developing vasoplegic syndrome[11,14,20]. Transfusion of blood products was higher in the CPB group. Despite the well-established exacerbation of postoperative inflammatory response in patients undergoing blood transfusions, available data regarding the correlation between the number of transfused blood products and incidence of postoperative vasoplegic syndrome is conflicting[11,12,14,15,20]. Current risk factors for the development of postoperative vasoplegia have not been fully elucidated. Most authors seem

to agree that preoperative use of ACE inhibitors, or heparin, increases the risk of vasoplegia[16]. Other preoperative factors with conflicting data are the use of beta-blockers, diabetes, and severe left ventricular dysfunction[11-15,20,21]. Surgical trauma itself may be responsible for some reported series of vasoplegia after off-pump cardiovascular surgeries[22]. Treatment of patients with vasoplegic syndrome in our study consisted of vasopressor support (norepinephrine, epinephrine and vasopressin) and methylene blue[12,16,23]. The only patient with vasoplegia in the off-pump group showed gradual improvement, with recovery of severe vasodilation within 36 hours. Overall mortality was high in the vasoplegic patients (42.86%), accounting for three of the seven in-hospital deaths in our study. Specific mortality was 50% for the CPB vasoplegic subgroup, and 0% for the off-pump vasoplegic subgroup. Our vasoplegic syndrome mortality was higher than the 25% rate usually published for patients with severe refractory vasodilation for more than 48 hours[12,13]. The pathophysiological mechanisms of vasoplegic syndrome remain controversial; however, there is clear association between pro-inflammatory mediators’ production and subsequent induction of nitric oxide production and GMPc mediated severe vasodilation. The rational use of vasopressin and methylene blue is based upon nitric oxide inhibition. Nevertheless, other pathways not directly related to nitric oxide release have been described, such as the direct activation of the final common pathway of vasodilation through guanylate cyclase enzyme, mediated by the release of pro-inflammatory molecules after CPB[11-13,24]. This pathway may explain the inconsistent reports of decreased mortality in vasoplegic syndrome with the use of vasopressin and methylene blue[16,23,25]. Considering the available data, an increased inflammatory response is clearly acting as a common pathophysiological role for the development of vasoplegic syndrome after cardiac surgery. The well described inflammatory reaction after the use of CPB coupled with the intrinsic status of chronic inflammation in patients with CRF, particularly hemodialysis, suggest that this combination of factors may complete the inflammatory equation that could explain a higher incidence of vasoplegia observed in the group of patients who underwent CPB in our data. Thus, our results support the current guidelines recommendation to perform off-pump CABG in patients with chronic renal failure requiring dialytic therapy. Study limitations We performed a retrospective analysis with a relatively small number of patients. Moreover, the common exclusion of these patients from larger trials may also interfere in the choice of the best surgical technique and results. Prospective studies with larger numbers of patients are needed to support our results.

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CONCLUSION Coronary artery bypass grafting with cardiopulmonary bypass in patients with chronic renal failure requiring dialysis therapy was an independent risk factor for the development of vasoplegic postoperative syndrome. Off-pump coronary artery bypass surgery seems to be a friendly alternative for the treatment of these patients.

5. Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg. 2002;21(2):232-44. 6. Brasil LA, Gomes WJ, Salomão R, Buffolo E. Inflammatory response after myocardial revascularization with or without cardiopulmonary bypass.Ann Thorac Surg. 1998;66(1):56-9. 7. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI), Kolh P, Wijns W, Danchin N, Di Mario C, Falk V, Folliguet T, et al. Guidelines on myocardial revascularization. Eur Heart J. 2010; 38 Suppl:S1-S52.

Authors’ roles & responsibilities NAHJ

MM MRM JNRB

GFV JOMAP WJG

Analysis and/or data interpretation; conception and design study; final manuscript approval; manuscript writing or critical review of its content; conduct of operations and/or trials; statistical analysis Analysis and/or data interpretation; conception and design study; final manuscript approval; manuscript writing or critical review of its content; statistical analysis Analysis and/or data interpretation, conception and design study; final manuscript approval; manuscript writing or critical review of its content Analysis and/or data interpretation; conception and design study; final manuscript approval; manuscript writing or critical review of its content; conduct of operations and/or trials; statistical analysis Final manuscript approval; manuscript writing or critical review of its content; conduct of operations and/or trials Analysis and/or data interpretation; conception and design study; final manuscript approval; manuscript writing or critical review of its content Analysis and/or data interpretation; final manuscript approval; manuscript writing or critical review of its content

8. Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011;124(23):2610-42. 9. Gomes WJ, Carvalho AC, Palma JH, Gonçalves I Jr, Buffolo E. Vasoplegic syndrome: a new dilemma. J Thorac Cardiovasc Surg. 1994;107(3):942-3. 10. Gomes WJ, Carvalho AC, Palma JH, Teles CA, Branco JN, Silas MG, et al. Vasoplegic syndrome after open heart surgery. J Cardiovasc Surg (Torino). 1998;39(5):619-23.

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compared with isolated on-pump CABG surgery? Cardiovasc Revasc Med. 2011;12(4):203-9. 22. Gomes WJ, Erlichman MR, Batista-Filho ML, Knobel M, Almeida DR, Carvalho AC, et al. Vasoplegic syndrome after off-pump coronary artery bypass surgery. Eur J Cardiothorac Surg. 2003;23(2):165-9.

18. Nashef SA, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, et al. EuroSCORE II. Eur J Cardiothorac Surg. 2012;41(4):734-44. 19. Delgado DS, Gerola LR, Hossne NA Jr, Branco JN, Buffolo E. Myocardial revascularization in renal transplant patients. Arq Bras Cardiol. 2002;79(5):476-83.

23. Leyh RG, Kofidis T, Str端ber M, Fischer S, Knobloch K, Wachsmann B, et al. Methylene blue: The drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass? J Thorac Cardiovasc Surg. 2003;125(6):1426-31.

20. Ascione R, Lloyd CT, Underwood MJ, Lotto AA, Pitsis AA, Angelini GD. Inflammatory response after coronary revascularization with or without cardiopulmonary bypass. Ann Thorac Surg. 2000;69(4):1198-204.

24. Nee L, Giorgi R, Garibaldi V, Bruzzese L, Blayac D, Fromonot J, et al. Ischemia-modified albumin and adenosine plasma concentrations are associated with severe systemic inflammatory response syndrome after cardiopulmonary bypass. J Crit Care. 2013;28(5):747-55.

21. Sun X, Boyce SW, Herr DL, Hill PC, Zhang L, Corso PJ, et al. Is vasoplegic syndrome more prevalent with open-heart procedures

25. Shanmugam G. Vasoplegic syndrome--the role of methylene blue. Eur J Cardiothorac Surg. 2005;28(5):705-10.

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Yuan SM - Sternal wound tuberculosis REVIEW ARTICLE following cardiac operations: a review

Sternal wound tuberculosis following cardiac operations: a review Tuberculose na ferida esternal após operações cardíacas: uma revisão

Shi-Min Yuan1, MMed, PhD

DOI: 10.5935/1678-9741.20140102

RBCCV 44205-1668

Abstract Objective: The diagnosis and treatment of sternal wound infections with mycobacteria are challenging. Such an infection is often associated with a delayed diagnosis and improper treatment that may lead to a worsened clinical outcome. The present study is designed to highlight its clinical features so as to facilitate a prompt diagnosis and timely treatment. Methods: MEDLINE, Highwire Press, and Google search engine were searched for publications in the English language, with no time limit, reporting on sternal wound infection caused by tuberculosis after cardiac surgery. Results: A total of 12 articles reporting on 14 patients were included in this study. Coronary artery bypass grafting was the underlying surgical procedure in more than half of the cases. Purulent discharge and cold abscess were the two main presenting symptoms. Diagnosis of sternal wound infection was evidenced in all 14 patients by different investigations, with culture of samples being the most sensitive method of identifying the pathogen. Good response to first-line anti-tuberculous agents was noted. Almost all patients required surgical debridement/ resection and, sometimes, sternal reconstruction. A delayed diagnosis of sternal wound infection may lead to repeated recurrences. A comparison between patients with sternal wound infection due to tuberculosis and non-tuberculous mycobacterial infections showed that the former infections took an even longer period of time. Comparisons also revealed patients

with sternal tuberculosis infection had a significantly higher mortality than patients with sternal non-tuberculous infection (29.2% vs. 0%, P=0.051). Conclusion: Sternal infection caused by tuberculosis after cardiac surgery has a longer latency, better response to first-line drugs, and better outcomes in comparison with non-tuberculous sternal infection. Early diagnosis and early anti-tuberculous treatment can surely improve the patients’ prognosis.

The First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, China.

Correspondence address: Shi-Min Yuan Longdejing Street, 389 - Chengxiang District, Putian, Fujian Province, People’s Republic of China E-mail: shi_min_yuan@yahoo.com

Descriptors: Sternum. Surgical Wound Infection. Tuberculosis. Resumo Objetivo: O diagnóstico e tratamento da infecção esternal com micobactérias são desafiadores. Essa infecção é muitas vezes associada a um diagnóstico tardio e o tratamento inadequado que pode levar a um resultado clínico pior. O presente estudo tem como objetivo destacar suas características clínicas, a fim de facilitar um diagnóstico rápido e tratamento adequado em tempo hábil. Métodos: MEDLINE, Highwire Press, e o mecanismo de busca Google foram pesquisados ​​por publicações em Inglês, sem limite de tempo, relatando sobre infecção de ferida esternal causada por tuberculose após cirurgia cardíaca. Resultados: Um total de 12 artigos, descrevendo 14 pacientes, foram incluídos no estudo. A revascularização do miocárdio

1

Work carried out at First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, Fujian Province, People’s Republic of China.

Article received on April 24th, 2014 Article accepted on August 4th, 2014

No financial support.

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foi o procedimento cirúrgico subjacente em mais da metade dos casos. Secreção purulenta e abscesso frio foram os dois principais sintomas apresentados. O diagnóstico de infecção de ferida esternal foi evidenciado em todos os 14 pacientes por diferentes investigações, com a cultura de amostras sendo o método mais sensível para identificar o agente patogênico. Boa resposta a agentes antituberculosos de primeira linha foi observada. Quase todos os pacientes necessitaram de desbridamento cirúrgico/ressecção e, em alguns casos, reconstrução esternal. Um diagnóstico tardio da infecção de ferida esternal pode levar a recorrências repetidas. Uma comparação entre pacientes com infecção de ferida esternal devido a infecções tuberculosas e micobactérias não tuberculosas mostrou que as infecções por tuberculose duraram um período de tempo maior. Comparações também revelaram

que pacientes com infecção esternal por tuberculose tiveram mortalidade significativamente mais elevada do que os pacientes com infecção esternal por micobactérias não tuberculosas (29,2% vs. 0%; P=0,051). Conclusão: A infecção esternal por tuberculose após cirurgia cardíaca tem uma latência maior, melhor resposta aos medicamentos de primeira linha e melhores resultados em comparação com a infecção esternal por micobactérias não tuberculosas. O diagnóstico precoce e o rápido tratamento antituberculose podem certamente melhorar o prognóstico dos pacientes. Descritores: Esterno. Infecção da Ferida Operatória. Tuberculose.

INTRODUCTION

no time limit, reporting on sternal wound infection caused by tuberculosis after cardiac surgery. The terms “tuberculosis” and “coronary artery bypass”, “heart valve replacement”, “heart valve prosthesis”, “heart valve repair”, “sternotomy”, “open heart surgery”, and “cardiothoracic surgery” were employed for the searches. All the articles, titles, and subject headings were carefully screened for potential relevance. Sternal wound infections caused by non-tuberculous mycobacteria were excluded. Due to the rarity of the condition, all the discovered articles reported only sporadic single or small series without a large population. Data were extracted mainly from the text. Variables included study population, demographics, clinical manifestations of sternal infection, predisposing risk factors, previous heart surgery, interval between cardiac surgery and sternal infection, sites of infections, diagnostic imaging, pathogen investigations, and anti-tuberculosis as well as surgical management strategies, length of follow-up, and main outcomes. Numerical data were expressed as mean±SD and compared with the independent samples t-test. Count data were expressed as percentages and compared with the Fisher’s exact test. Results with P<0.05 was considered statistically significant.

Mediastinitis is a serious complication of median sternotomy and is associated with significant morbidity and mortality[1]. Although sternal wound infections after cardiac operations through median sternotomy are uncommon, with a prevalence of only 0.4-5.0% of the cases[2], they are associated with increased morbidity, prolonged hospital stay, and increased costs[3]. The risk factors of sternal wound infections have been sufficiently described[4-7]. The most common causative pathogen was Staphylococcus aureus, accounting for 28-58.1%, followed by Acinetobacter spp (20%)[8-10]. Surgical wound infection caused by mycobacterium tuberculosis is extremely rare[11]. The exact prevalence remains uncertain; however, it has been estimated that sternal tuberculosis infection accounted for 4.1% of sternal wound infections after open heart surgery[12]. Recently, Unai et al.[13] comprehensively studied the sternal wound infection caused by non-tuberculous mycobacteria, providing some detailed information on the patient. Nevertheless, there remains no clear consensus on sternal wound infection caused by tuberculosis after Wang et al.[11] presented information of six patients. The diagnosis and treatment of sternal wound infections with mycobacteria are challenging. Such an infection is often associated with a delayed diagnosis and improper treatment that may lead to a worsened clinical outcome. Therefore, it is important for the physicians to bear in mind the clinical features of this rare infection. The aim of the present article is to make a comprehensive analysis of sternal wound infection caused by tuberculosis after cardiac surgery and compare it to the data available from the report by Unai et al.[13] on sternal wound infections caused by non-tuberculous mycobacteria.

RESULTS Information on a total of 15 patients from 13 articles[11,12,14-24] were collected. Data from repetitive descriptions of the same patient in 2 articles[23,24] were incorporated. As a result, 12 articles reporting on 14 patients were included in this study. The 12 articles were comprised of 10 case reports[11,14-21,23] and 2 original articles[12,22]. Gender of 11 patients was described, including 8 (72.7%) males and 3 (27.3%) females. The patients' age was 58.6±15.3 (range, 16-72; median, 60) years (n=11). The underlying surgical procedures were coronary artery bypass grafting in 8 patients (57.1%),

METHODS MEDLINE, Highwire Press, and Google search engine were searched for publications in the English language, with

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open heart surgery (unspecified) in 3 patients (21.4%) as well as aortic valve replacement, mitral valve repair, redo-Bentall operation, and cardiothoracic surgery (unspecified) in 1 (7.1%) patient each, respectively. The interval between heart surgery and sternal infection was 13.3±17.1 (range, 0.5-60; median, 7) months (n=11). The symptoms were described in 12 patients and included purulent discharge in 7 (58.3%), cold abscess in 4 (33.3%), subcutaneous sinus in 3 (33.3%), local pain in 2 (16.7%), fever in 2 (16.7%), sternal swelling in 1 (8.3%), sternal mass in 1 (8.3%), and symptoms irrelevant to sternal wound infections in 2 (16.7%) patients. In 6 (42.9%) patients, one or more predictive risk factors for sternal wound infection were determined, which were diabetes mellitus in 4 (66.7%) (of those, one patient was also associated with hypertension, hyperlipidemia, and diabetic nephropathy requiring persisted dialysis, and another patient was associated with lung tuberculosis) and tuberculosis contact in 2 (33.3%) patients. The locations of infections in the sternum were described in 6 patients, including 1 (16.7%) in the manubrium[16], 1 (16.7%) in the upper portion[18], 2 (33.3%) in the lower portion[11,15], 1 (16.7%) in the body of the sternum[20], and 1 (16.7%) that was described as “9 cm below the suprasternal notch”[14]. Sternal destruction was noted on chest X-ray and on chest computed tomography in 2 (14.3%) patients each. Lymphadenopathy was noted in 3 (21.4%) patients: cervical[16], hilar and subcarinal[21], and scattered visceral lymphadenopathy[23] in 1 patient each. Diagnosis of sternal wound infection was evidenced in all 14 patients by different investigations, with culture of samples being the most sensitive method for identifying the pathogen (Table 1). Associated Staphylococcus aureus infection was found in 2 patients[11,15]. Anti-tuberculous treatment was indicated in

12 patients. One of them received an adjusted anti-tuberculous regimen due to end-stage renal failure, gastrointestinal upset, and thrombocytopenia[11]. Duration of anti-tuberculous treatment was 10.8±1.6 (range, 9-12; median, 12) months (n=5). Anti-tuberculous therapy took effect within various time intervals, either rapidly[23] or over a few weeks[16]. Discharge from the sinus stopped in 15 days and the sinus healed after 2 months[14]. Surgical operation was performed in 13 patients: debridement in 6 (46.2%)[11,14,16,18,21,22], extensive resection with chest wall reconstruction in 5 (38.5%)[15,19,20,23], and the surgical procedure was not indicated in 2 (15.4%) patients[12]. The chest reconstruction materials were pectoralis (major) flap in 3 (60%)[15,19,20], omental flap interposition plus titanium plate in 1 (20%)[23], and pectoralis major myocutaneous flap in stage 1 and omental flap in stage 2 operation in 1 (20%) patient[23]. The patients were at a follow-up of 9±3.9 (range, 3-14; median, 9) months (n=9). Prognosis was not reported in 2 patients[19,22]. All the remaining 12 patients survived. However, before a full recovery, 3 (25%) patients had 1-2 recurrences due to an up to 2-year delay in the diagnosis of tuberculous infection[14,17,18]. DISCUSSION Dissemination of tuberculosis include spread as a late complication of pulmonary tuberculous, reactivation of latent foci formed during hematogenous or lymphatic dissemination of primary tuberculosis, or direct extension from mediastinal lymph nodes[25]. Skeletal tuberculosis accounted for approximately 6-10% of extrapulmonary tuberculous cases and 1% of all tuberculous cases, and sternal tuberculosis is involved in approximately 1% of

Table 1. Investigations of samples for the diagnosis of sternal wound tuberculosis infection. Investigation Sample Cultures Intraoperative resected/debridged tissue Sternal pus/discharge Ascites Sputum Unspecified Histopathology Intraoperative resected/debrided para-sternal tissue Fine needle aspiration of cervical lymph nodes Resected pulmonary lesion Intraoperative frozen nodule biopsy Unspecified specimens Ziehl-Neelsen stain Intraoperative resected/debridged specimens Sputum & pus Polymerase chain reaction Debrided tissue

Reference n (%) 12 (85.7)* 7 (58.3) [11,14,15,18-21,23] [17,18,22] 3 (25) [23] 1 (8.3) [17] 1 (8.3) [12] 2 (16.7) 9 (64.3) [11,14,19,20] 4 (44.4) [16] 1 (11.1) [17] 1 (11.1) [23] 1 (11.1) [12] 2 (22.2) 3 (21.4) [11,19] 2 (66.7) [17] 1 (33.3) 1 (7.1) [11] 1 (100)

*There were a total of 14 samples for mycobacterial cultures from 12 patients.

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Table 2. A comparison between tuberculous and non-tuberculous mycobacterial sternal infections. Variable Patients’ age Gender (male/female) Latency from cardiac surgery to sternal infection (month) Purulent discharge Mortality

TB 58.6±15.3 8/3 13.3±17.1 7/13 0/12

NTB 55.3±16.6 43/16 1.4±1.1 27/38 14/48

P value 0.619 0.521 0.044 0.315 0.051

NTB=non-tuberculosis; TB=tuberculosis

skeletal tuberculosis cases[26]. Sternal infection due to tuberculosis after cardiac surgery is even rarer. Mycobacterium tuberculosis is a member of the slow-growing pathogenic mycobacterial species, characterized by a 12- to 24-hour division rate and prolonged culture period on agar of up to 21 days[27]. Hosts of tuberculous infections may be in a latent period with no symptoms for years or decades, allowing the establishment of a chronic asymptomatic infection, followed by reactivation and transmission years later to new uninfected hosts[27]. This study showed that 8 (57.1%) patients with sternal wound infection caused by tuberculosis had a history of coronary artery bypass grafting. The most common manifestation was purulent discharge, followed by cold abscess. The diagnosis of sternal infection due to tuberculosis can be made primarily from the bony destruction, and eventually it will depend on pathogen investigations by culture and histopathology of aspirated/debrided/resected tissue. Besides, Ziehl-Neelsen stain and polymerase chain reaction can be valuable for pathogen screening. Delayed diagnoses may lead to recurrence and protracted course of disease. All patients responded well to first-line anti-tuberculous drugs. Most of the patients required surgical treatment, with nearly half requiring extensive resection with chest wall reconstruction. Rapidly growing mycobacteria is largely present in our living environment. It is usually resistant to first-line anti-tuberculosis agents[28] in addition to being commonly resistant to sterilizers, disinfectants, and antiseptics[29]. Therefore, non-tuberculous mycobacteria may contaminate medical devices such as heart valve prosthesis, and it can be associated with nosocomial outbreaks. The average time from the operation to sternal non-tuberculous mycobacterial infection was 64.1±84.6 (range, 24330; median, 30) days[13], which seems to be longer than the latency of 1-2 months of usual bacterial mediastinitis[3]. The present study demonstrated that the sternal infections caused by tuberculosis required an even longer time to develop than sternal infections with non-tuberculous mycobacteria. Comparisons also revealed patients with sternal infection caused by non-tuberculous mycobacteria had significantly higher

mortality rates than patients with sternal infection due to tuberculosis (29.2% vs. 0%, P=0.051) (Table 2). In general, sternal infection caused by tuberculosis after cardiac surgery has longer latency, better response to firstline drugs, and better outcomes in comparison with sternal infection caused by non-tuberculous mycobacteria. Early diagnosis and early anti-tuberculous treatment can surely improve the patients’ prognosis. Authors’ roles & responsibilities SMY

Study conception and design; analysis and/or interpretation of data; manuscript writing.

REFERENCES 1. Sá MP, Soares EF, Santos CA, Figueiredo OJ, Lima RO, Escobar RR, et al. Skeletonized left internal thoracic artery is associated with lower rates of mediastinitis in diabetic patients. Rev Bras Cir Cardiovasc. 2011;26(2):183-9. 2. Sarr MG, Gott VL, Townsend TR. Mediastinal infection after cardiac surgery. Ann Thorac Surg. 1984;38(4):415-23. 3. Shi YD, Qi FZ, Zhang Y. Treatment of sternal wound infections after open-heart surgery. Asian J Surg. 2014;37(1):24-9. 4. Magedanz EH, Bodanese LC, Guaragna JC, Albuquerque LC, Martins V, Minossi SD, et al. Risk score elaboration for mediastinitis after coronary artery bypass grafting. Rev Bras Cir Cardiovasc. 2010;25(2):154-9. 5. Tiveron MG, Fiorelli AI, Mota EM, Mejia OA, Brandão CM, Dallan LA, et al. Preoperative risk factors for mediastinitis after cardiac surgery: analysis of 2768 patients. Rev Bras Cir Cardiovasc. 2012;27(2):203-10. 6. Sá MP, Figueira ES, Santos CA, Figueiredo OJ, Lima RO, Rueda FG, et al. Validation of MagedanzSCORE as a predictor of mediastinitis after coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2011;26(3):386-92.

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7. Sรก MP, Santos CA, Figueiredo OJ, Lima RO, Ferraz PE, Soares AM, et al. Skeletonized internal thoracic artery is associated with lower rates of mediastinitis in elderly undergoing coronary artery bypass grafting surgery. Rev Bras Cir Cardiovasc. 2011;26(4):617-23.

18. Achouh P, Aoun N, Hagege A, Fabiani JN. Mediastinitis due to Mycobacterium tuberculosis after a redo open heart surgery. J Cardiovasc Surg (Torino). 2005;46(1):93-4. 19. Rivas P, Gรณrgolas M, Gimena B, Sousa J, Fernรกndez-Guerrero ML. Sternal tuberculosis after open heart surgery. Scand J Infect Dis. 2005;37(5):373-4.

8. Gib MC, Alvarez JS, Wender OC. Mediastinitis: mortality rate comparing single-stage surgical approach and preconditioning of wound. Rev Bras Cir Cardiovasc. 2013;28(2):200-7.

20. Gopal K, Raj A, Rajesh MR, Prabhu SK, Geothe J. Sternal tuberculosis after sternotomy for coronary artery bypass surgery: a case report and review of the literature. J Thorac Cardiovasc Surg. 2007;133(5):1365-6.

9. Sรก MP, Silva DO, Lima EN, Lima Rde C, Silva FP, Rueda FG, et al. Postoperative mediastinitis in cardiovascular surgery. Analysis of 1038 consecutive surgeries. Rev Bras Cir Cardiovasc. 2010;25(1):19-24.

21. Patel P, Tabasi ST. Sternal osteomyelitis caused by mycobacterium tuberculosis after open heart surgery. Infect Dis Clin Pract. 2011;19(5):359-61.

10. Sรก MP, Soares EF, Santos CA, Figueiredo OJ, Lima RO, Escobar RR, et al. Risk factors for mediastinitis after coronary artery bypass grafting surgery. Rev Bras Cir Cardiovasc. 2011;26(1):27-35.

22. Yu WK, Chen YW, Shie HG, Lien TC, Kao HK, Wang JH. Hyperbaric oxygen therapy as an adjunctive treatment for sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery. J Cardiothorac Surg. 2011;6:141.

11. Wang TK, Wong CF, Au WK, Cheng VC, Wong SS. Mycobacterium tuberculosis sternal wound infection after open heart surgery: a case report and review of the literature. Diagn Microbiol Infect Dis. 2007;58(2):245-9.

23. Kim HJ, Kim JB, Chung CH. Chronic sternum wound infection caused by Mycobacterium tuberculosis after cardiac surgery. Ann Thorac Surg. 2012;94(4):1332-5.

12. Okonta KE, Anbarasu M, Agarwal V, Jamesraj J, Kurian VM, Rajan S. Sternal wound infection following open heart surgery: appraisal of incidence, risk factors, changing bacteriologic pattern and treatment outcome. Indian J Thorac Cardiovasc Surg. 2011; 27(1):28-32.

24. Kim WK, Kim JB, Kim GS, Jung SH, Choo SJ, Chung CH, et al. Titanium plate fixation for sternal dehiscence in major cardiac surgery. Korean J Thorac Cardiovasc Surg. 2013;46(4):279-84. 25. Khan SA, Varshney MK, Hasan AS, Kumar A, Trikha V. Tuberculosis of the sternum: a clinical study. J Bone Joint Surg Br. 2007;89(6):817-20.

13. Unai S, Miessau J, Karbowski P, Bajwa G, Hirose H. Sternal wound infection caused by Mycobacterium chelonae. J Card Surg. 2013;28(6):687-92.

26. Vasa M, Ohikhuare C, Brickner L. Primary sternal tuberculosis osteomyelitis: a case report and discussion. Can J Infect Dis Med Microbiol. 2009;20(4):e181-4.

14. Damle AS, Karyakarte RP, Bansal MP. Tuberculosis infection in post-operative wound. Ind J Tuberc. 1995;42(3):177-8. 15. Rubinstien EM, Lehmann T. Sternal osteomyelitis due to Mycobacterium tuberculosis following coronary artery bypass surgery. Clin Infect Dis. 1996;23(1):202-3.

27. Sakamoto K. The pathology of Mycobacterium tuberculosis infection. Vet Pathol. 2012;49(3):423-39.

16. Aggarwal B, Kamath S, Shatapathy P. Tubercular sternal osteomyelitis and mediastinitis after open heart surgery. Indian Heart J. 1997;49(3):313-4.

28. Chopra S, Matsuyama K, Hutson C, Madrid P. Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae. J Antimicrob Chemother. 2011;66(7):1533-6.

17. Sipsas NV, Panayiotakopoulos GD, Zormpala A, Thanos L, Artinopoulos C, Kordossis T. Sternal tuberculosis after coronary artery bypass graft surgery. Scand J Infect Dis. 2001;33(5):387-8.

29. Shah P, Vishnevsky A. Mycobacterium fortuitum device infection with subsequent endocarditis. Medicine Forum. 2012;13:Article 13 [Accessed June 26, 2014]. Available at: http://jdc.jefferson. edu/tmf/vol13/iss1/13

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Hostiuc S,BRIEF et al. - Aortic rupture during reoperative bariatric surgery COMMUNICATION

Aortic rupture during reoperative bariatric surgery Ruptura da aorta durante a cirurgia bariátrica

Sorin Hostiuc1, MD, PhD; Constantin Dragoteanu2, MD; Victor Asavei3; Ionut Negoi1, MD, PhD

DOI: 10.5935/1678-9741.20150051

RBCCV 44205-1669

Abstract Morbid obesity has become a very common problem worldwide, causing severe health-related consequences including cardiovascular or metabolic diseases, arthritis, sleep apnea, or an increased risk of cancer. Bariatric surgery was shown to be the only way to achieve sustainable weight loss and to decrease the frequency and severity of metabolic and cardiovascular comorbidities. The purpose of this article is to present a case of bariatric surgery complicated with lesion of the aorta with a lethal outcome.

Resumo A obesidade mórbida é cada vez mais comum em todo o mundo, causando graves consequências relacionadas com a saúde, incluindo doenças cardiovasculares ou metabólicas, artrite, apneia do sono, ou um aumento do risco de câncer. A cirurgia bariátrica mostrou ser a única maneira de conseguir a perda de peso sustentável e para diminuir a frequência e a gravidade das comorbidades metabólicas e cardiovasculares. O objetivo deste artigo é apresentar um caso de cirurgia bariátrica que provocou lesão da aorta com um desfecho letal.

Descriptors: Bariatric Surgery. Obesity, Morbid. Aorta/ Injuries.

Descritores: Cirurgia Bariátrica. Obesidade Mórbida. Aorta/Lesões.

INTRODUCTION

though others such as the Roux-en-Y gastric bypass or biliopancreatic diversion are still performed[2]. The mortality rate in bariatric surgery is between 0.05 and 2%, the most frequent cause of death being an anastomotic leak with subsequent infection[4]. Overall, between 10 and 25% of all bariatric patients need a revision surgery for failure of the primary procedure, either determined by inadequate weight loss or surgical complications[5]. The mortality is increased if revision surgery is needed[6]. The purpose of this article is to present a potential complication of abdominal surgery re-entry for gastric band correction at the level of the aorta having in the end a lethal outcome.

Morbid obesity has become a very common problem worldwide, causing severe health-related consequences including cardiovascular or metabolic diseases, arthritis, sleep apnea, or an increased risk of cancer[1]. Bariatric surgery was shown to be the only way to achieve sustainable weight loss and to decrease the frequency and severity of metabolic and cardiovascular comorbidities[2]. Laparoscopic adjustable gastric band (LAGB) is in many countries, especially in Europe and Australia[3], the most frequently used technique[2], even

Carol Davila University of Medicine and Pharmacy - Floreasca Clinical Emergency Hospital,Department of Surgery, Bucharest, Romania. 2 National Institute of Legal Medicine, Department of Forensic Pathology, Bucharest, Romania. 3 Polytechnic University, Bucharest, Romania.

Financial support: The work has been funded by the Sectoral Operational Programme Human Resources Development 2007-2013 of the Ministry of European Funds through the Financial Agreement POSDRU/159/1.5/S/134398

1

Correspondence Address: Sorin Hostiuc 9 Vitan Barzesti Street, Bucharest, Romania - Zip code: 0422122 E-mail: soraer@gmail.com

This study was carried out at Carol Davila University of Medicine and Pharmacy - Floreasca Clinical Emergency Hospital, Department of Surgery, Bucharest, Romania.

Article received on January 27th, 2015 Article accepted on July 15th, 2015

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0.2 cm was identified, affecting the intima and partially the media. In the stomach, a callous ulcer near the pyloric antrum was identified on the posterior gastric wall, with rounded margins, affecting the mucosal, submucosal and muscular layer, with a diameter of about 1.5 cm. The esophagus in the subdiaphragmatic part, near the cardia, had an anfractuous laceration, affecting all the anatomical layers, with a sutured hemorrhagic infiltrate.

Abbreviations, acronyms & symbols LAGB

Laparoscopic adjustable gastric band

CASE REPORT A 26 years old woman with morbid obesity was admitted for bariatric surgery (laparoscopic adjustable gastric banding). The patient was released from the hospital after three days. After about four months she was admitted again, with an initial diagnosis of superior digestive hemorrhage and status post gastric banding. Clinically, the patient was conscious, cooperative, without signs of peritoneal irritation, with an arterial pressure of 110/60 mmHg. Radiological examination revealed an anteriorly malrotated ring, intraparietal filling with a radiopaque material, and a small retro-parietal fistula in the gastric fundus. As the patient presented superior digestive hemorrhage and ring malrotation a surgical intervention was performed, whose aim was to extract the band. Laparoscopy was performed with the trocars located above the umbilicus, in the left flank, left and right hypochondriac area, and in the epigastrium. During the surgical intervention, the rubber hose of the ring was associated a severe inflammatory reaction, incorporating the abdominal esophagus, the cardiac area of the stomach, and the celiac region. A difficult sharp dissection was started for viscerolysis; while trying to mobilize the ring that was identified red, arterial blood flowing through the nasogastric tube. The procedure was immediately converted to a xiphoid-umbilical laparotomy associated with gastrotomy step in which were evacuated large blood clots from the stomach; the source of bleeding was found to be a laceration of about two centimeters at the anterior part of the aorta, located posteriorly from the esophagus. At the same time the anesthetic team, noticing 600 ml of fresh blood in the aspirator of the gastric content started the resuscitation protocol. After laparotomy, another 1800 ml fresh blood was aspirated from the surgical field. There was not an available cell saver in the operating room. Due to the severity of the intraoperative incident, together with the scarce reserve of the hospital blood supplies, the patient received only four units of packed red blood cells and five units of fresh frozen plasma. The laceration was sutured but the blood losses were too great and the patient died of hemorrhagic shock, unresponsive to resuscitation maneuvers.

Fig. 1 - Iatrogenic aortic injury, as observed during the autopsy.

Histology examination confirmed the laceration, affecting all the layers of the aortic wall, with small hemorrhagic areas in the media, and abundant inflammatory reaction with lymphocytes and plasma cells, located around the vasa vasorum and in the surrounding interstitial tissue. The esophagus contained numerous, recent hemorrhagic areas mostly located between the adventitial and muscle layers, with a chronic inflammatory reaction (lymphocytes and plasma cells) in the muscle and subadventitial layers. The stomach contained an unspecific gastritis with large ulcero-necrotic areas, abundant chronic inflammatory reaction in the interstitial and perivascular areas of the submucosa, muscularis propria, and subserous layers, with immature granular tissue in the subserous layer and acute inflammatory reaction at the serous layer (non-steroidal anti-inflammatory associated gastritis). The cause of death was considered acute hemorrhage (Ia), secondary to an aortic rupture during bariatric surgery.

Autopsy findings On the anterior side of the lower part of the thoracic aorta, near the diaphragm, an H laceration of about 1.2/1cm was identified, with an irregular contour and hemorrhagic infiltrate (Figure 1). On the posterior side of the aorta, corresponding to the anterior lesion, a small laceration of about

Ethics The management of ethics related issues was performed in accordance with the Romanian Law regarding the organization and functioning of the medical legal system No 1 from

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20.01.2000, Art 2(3) and Art 15(e) and Decision No.774/2000 regarding the approval of the methodological norms for the application of the Law 1/200, Art 39(1), in full compliance with relevant international norms, including the Declaration of Helsinki. Both surgeries of the presented case were done in a tertiary surgical department, neither author being involved in the clinical management.

ACKNOWLEDGMENTS The work has been funded by the Sectoral Operational Programme Human Resources Development 2007-2013 of the Ministry of European Funds through the Financial Agreement POSDRU/159/1.5/S/134398.

DISCUSSION

Authors’ roles & responsibilities

Band slippage is a relatively frequent postoperative complication of LAGB, with an overall prevalence of about 5.5%[7]. If it is confirmed the first step is represented by band deflation through the subcutaneous port. However, in our case, the presence of superior digestive hemorrhage suggested the possibility of gastric erosion or ischemia, suggesting the need for a surgical re-intervention. During revision the surgeon must be aware that around the band is often encountered a fibrous reaction that requires careful dissection[2]. Moreover, aorta passes posteriorly of the stomach and esophagus, in close relation with these structures; therefore the fibrous tissue developed after bariatric surgery may have had a traction effect upon this vessel. There is no doubt that severe chronic inflammation, with dense adhesions between the band, the abdominal esophagus, the stomach and the abdominal aorta passing through its diaphragmatic hiatus played an important role for this major incident. The characteristics of the aorta rupture suggest iatrogenic lesions during gastric dissection, most likely done by a sharp object (e.g. scizzors), that could also explain the presence of the posterior aorta lesion. Aortic complications secondary to bariatric surgery have been rarely cited. Gaia cited a case of ruptured aortic aneurism and an aortic dissection in patients that underwent a bariatric procedure[8]; however they were not caused by the intervention per se or its complications, being most likely associated with the comorbidities of morbid obesity (atherosclerosis, aortic calcifications, and so on). This is the first reported case, to our knowledge, of an intraoperative aortic lesion secondary to a repositioning procedure for a gastric band.

SH CD VA IN

Analysis and/or interpretation of data; final manuscript approval; manuscript writing or critical review of its content Analysis and/or interpretation of data; final manuscript approval; manuscript writing or critical review of its content Analysis and/or interpretation of data; final manuscript approval; manuscript writing or critical review of its content Analysis and/or interpretation of data; statistical analysis; final manuscript approval; study design; manuscript writing or critical review of its content

REFERENCES 1. Lee CW, Kelly JJ, Wassef WY. Complications of bariatric surgery. Curr Opin Gastroenterol. 2007;23(6):636-43. 2. Monkhouse SJ, Morgan JD, Norton SA. Complications of bariatric surgery: presentation and emergency management: a review. Ann R Coll Surg Engl. 2009;91(4):280-6. 3. Franco JV, Ruiz PA, Palermo M, Gagner M. A review of studies comparing three laparoscopic procedures in bariatric surgery: sleeve gastrectomy, Roux-en-Y gastric bypass and adjustable gastric banding. Obes Surg. 2011;21(9):1458-68. 4. Goldfeder LB, Ren CJ, Gill JR. Fatal complications of bariatric surgery. Obes Surg. 2006;16(8):1050-6. 5. Benedix F, Scheidbach H, Arend J, Lippert H, Wolff S. Revision after failed bariatric surgery: review of complications and current therapeutic options. Zentralbl Chir. 2009;134(3):214-24. 6. Owens BM, Owens ML, Hill CW. Effect of revisional bariatric surgery on weight loss and frequency of complications. Obes Surg. 1996;6(6):479-84.

CONCLUSION

7. Karpitschka M, Lang R, Jauch KW, Reiser MF, Weckbach S. Bariatric surgery and associated complications: radiological imaging. Radiologe. 2011;51(5):352-65.

The morbid obesity surgeries, especially revision surgeries, carry a high morbidity and even mortality. Only a thorough preoperative planning, a careful operative technique, and a low threshold for conversion to open surgery may decrease the failure rate of these surgeries.

8. Gaia DF, Palma JH, Branco JN, Buffolo E. Aortic complications after bariatric surgery. Rev Bras Cir Cardiovasc. 2008;23(3):415-7.

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Guida M, et al.HOW-TO-DO-IT - Off-pump bidirectional Glenn through right anterior thoracotomy

Off-pump bidirectional Glenn through right anterior thoracotomy Glenn bidirecional sem uso de CEC via toracotomia anterior direita

Maximo Guida1, MD, PhD; Andrea Lo Cascio1, MD; Gustavo Guida1, MD; Gabriel Guida1, MD; Estefania De Garate1, MD; Manuel Vasquez1, MD; Fernando Prieto1, MD, PhD; Miriam Pecchinenda1

DOI: 10.5935/1678-9741.20150047

RBCCV 44205-1670

Abstract The Glenn operation involving anastomosis of the superior vena cava to the pulmonary artery has been performed for palliative operations of many cyanotic congenital heart diseases in addition to the single ventricle since the 1960s. The classic procedure is done via median sternotomy and cardiopulmonary bypass. The benefits of this procedure without the use of cardiopulmonary bypass remain mixed within reported series. Cases using this approach and off-pump technique together in Latin-America have not yet been reported in the scientific literature.

Resumo A operação de Glenn envolvendo anastomose da veia cava superior à artéria pulmonar foi realizada como procedimento paliativo de muitas doenças cardíacas congênitas cianóticas, além do ventrículo único desde os anos 1960. O procedimento clássico é feito por esternotomia mediana e circulação extracorpórea. Os benefícios deste procedimento sem o uso de circulação extracorpórea permanecem incertos dentro da série relatada. Casos utilizando conjuntamente esta abordagem e a técnica sem circulação extracorpórea na América Latina ainda não foram relatados na literatura científica.

Descriptors: Cardiopulmonary Bypass. Anastomosis, Surgical. Thoracotomy. Heart Defects, Congenital. Cyanosis.

Descritores: Ponte Cardiopulmonar. Anastomose Cirúrgica. Toracotomia. Cardiopatias Congênitas. Cianose.

INTRODUCTION

Cases using this approach and off-pump technique together in Latin-America have not yet been reported in the scientific literature.

The Glenn operation involving anastomosis of the superior vena cava to the pulmonary artery has been performed for palliative operations of many cyanotic congenital heart diseases in addition to the single ventricle since the 1960s[1]. The classic procedure is done via median sternotomy and cardiopulmonary bypass[2,3] the benefits of this procedure without the use of cardiopulmonary bypass remain mixed within reported series because there are still controversial conclusions[4-6].

1

CASE REPORT A twenty-monthold male patient, body weighing 7 kg, diagnosed with pulmonary atresia (PA) ventricular septal defect (VSD) + pulmonary hypoplasia clinically presented with severe cyanosis, oxygen saturation (SaO2) of 35%, and history of generalized tonic-clonic seizure in several occasions, was

Fundacardio Foundation, Valencia, Venezuela.

Correspondence address: Maximo Guida Fundacardio Foundation - Valencia – Venezuela 137 Bolivar Norte Avenue - A Street, Camoruco Sector, Res. Pecchinenda D Planta Baja - Valencia, Venezuela E-mail: maximo_guida@hotmail.com

This study was carried out at Fundacardio Foundation, Valencia, Venezuela.

Article received on May 9th, 2015 Article accepted on July 6th, 2015

No financial support.

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the right atrial appendage. The patient was systemic heparinized with 300 units/kg to maintain activated coagulation time (ACT) above 250. A 12F right-angle cannula was placed high on the SVC and a 12F straight cannula was placed in the right atrium. These cannulas were de-aired and hooked together to create a venoatrial shunt and allow drainage of the upper body while the proximal SVC was occluded (Figure 2). The pulmonary artery was temporarily occluded using a partial clamp, to ensure acceptable oxygen saturations (maintained between 50-60%) and hemodynamic stability (Figure 3). The SVC was clamped and sectioned distally; the stump was oversewed using two layers of 6-0 polipropilene (Figure 4A).

Abbreviations, acronyms & symbols ABG Arterial blood gas ACT Activated coagulation time BGP Bidirectional Glenn procedure CPB Cardiopulmonary bypass ECG Electrocardiogram EtCO2 End-tidal carbon dioxide PA Pulmonary atresia RPA Right pulmonary artery Sa02 Oxygen saturation SVC Superior vena cava VSD Ventricular septum defect

referred to our service for a bidirectional Glenn procedure in order to improve his clinical condition; the Blalock-Taussing (BT) shunt was also considered, but our preference was the first procedure. The Ethics Commettee aproval was granted either for the use of whole medical history contents and the scientific use of the data. The patient’s relatives also signed an informed consent for the surgery and the use of both pictures and content for scientific purpose. Before surgery the patient had an angiogram with right heart catheterization to measure pulmonary artery pressure and also to determine whether the procedure was feasible. The procedure was performed under general anesthesia. The intraoperative management included monitoring electrocardiogram (ECG), SaO2, end-tidal carbon dioxide (EtCO2). Arterial blood gas (ABG) was analyzed at the baseline after intubation and during the procedure. In addition pressure monitoring line was placed in the superior vena cava (SVC), an invasive arterial pressure line was placed in the femoral artery and central venous access was obtained using a trilumen catheter into the right femoral vein, the corporal temperature was monitorized by rectal probe and controlled at 36oC with the use of a thermic mattress as well as the operation room’s temperature, all this as part of our usual surgical protocol. A right anterior thoracotomy was performed in the 4th intercostal space; after the pleural cavity was opened the right lung was partially retracted with the use of lap sponges, checking the oxygen saturation and hemodynamic stability (Figure 1). Circumferential control was gained around the entire length of the SVC, exposing this vessel completly by dissecting from the adjacent tissues. The azygous vein was ligated at this stage, this was to ensure non steal phenomenon from the SVC to inferior vena cava through this vein. The right pulmonary artery was exposed, and circumferential control was gained around the right main pulmonary artery as well as the hilar branches. Intraoperative pressure of the right pulmonary artery (RPA) was measured for the feasibility of the procedure. Two purse-string-sutures with 5-0 polipropilene were performed, one at the proximal side of the SVC and the other at

Fig. 1 - Approach - The picture presents first exposure of the superior vena cava and the right atrium.

Fig. 2 - SVC-RA shunt - In this picture the SVC-RA shunt is already set in position and working while the SVC-RPA anastomosis is performed. SVC-RA=superior vena cava and the right atrium; SVC-RPA=superior vena cava and right pulmonary artery

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Fig. 3 - SVC clamp - The picture presents the SVC clamped before the SVC-RPA anastomosis. SVC=superior vena cava; SVC-RPA=superior vena cava and right pulmonary artery

A

B

Fig. 4 - Final result - It is shown the SVC-RPA anastomosis and the RA stump in this picture. SVC-RPA=superior vena cava and right pulmonary artery; RA=right atrium

The SVC was anastomosed to the RPA using continuous 6-0 polipropilene suture; the clamps were removed and hemostasis achieved (Figure 4B). The shunt between the SVC and the right atrium was removed and the heparin reverted with protamine, finally the surgical incision was closed conventionally, the right pleura was drained using a single Blake system chest drain, connected to a conventional vacuum system. The patient was extubated in the operation room and the O2 saturation raised to 90%, the patient was then transferred to intensive care unit in stable general and hemodynamic conditions. The patient had a satisfactory recovery and was discharged on the 4th postoperative day in good general conditions.

DISCUSSION The bidirectional Glenn procedure (BGP) can be performed via median sternotomy or anterior right thoracotomy, furthermore the use of cardiopulmonary bypass or a temporary shunt between SVC and the right atrium can also be considered. The decision about the approach and strategy is mainly based on the surgical team experience, patient’s condition and the perioperative risk. Many published studies have shown good results when the cardiopulmonary bypass (CPB) is avoided[5,7]; furthermore the original surgical technique described by Glenn in 1958 was performed through a thoracotomy and without CPB[8].

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One of the concerns of using the veno-atrial shunt instead of CPB is the risk of inadequate brain protection, due to its flow capacity and the clamping time of the SCV[5,7]. One of the measures to improve the brain protection is clamping the SCV underneath the insertion of the azygos vein, as well as the use of a dopamine infusion and a good general circulation volume[5,7], all this to achieve a high transcraneal pressure gradient. The use of Fowler position in the operation table is also beneficial. Some authors have excluded patients with O2 saturation under 65%, because they considered it increases the risk for operative mortality[9]. The case we are presenting had an O2 saturation of 35% which according with the literature would be considered as a very high risk patient for this procedure. However, the postoperative course confirmed the feasibility of the technique. Avoiding the use of cardiopulmonary bypass has multiples advantages, especially in low weight patients, decreasing the deleterious effects produced on the rest of the organs and vital systems[10]. The right anterior thoracotomy approach represents a good choice for selected patients, leaving the median sternotomy available for future interventions. In this case the postoperative course was highly satisfactory and after ten months after surgery the patient remains in excellent clinical conditions, maintaining O2 saturation in ambient air above 85%.

REFERENCES 1. Trusler GA, MacGregor D, Mustard WT. Cavopulmonary anastomosis for cyanotic congenital heart disease. J Thorac Cardiovasc Surg. 1971;62(5):803-9. 2. Chaccur P, Dinkhuysen JJ, Abdulmassih Neto C, Arnoni AS, Silva MVD, Bosísio IJ, et al. Operação de Glenn bidirecional. Rev Bras Cir Cardiovasc. 1992;7(3):194-200. 3. Bertolizio G, DiNardo JA, Laussen PC, Polito A, Pigula FA, Zurakowski D, et al. Evaluation of cerebral oxygenation and perfusion with conversion from an arterial-to-systemic shunt circulation to the bidirectional Glenn circulation in patients with univentricular cardiac abnormalities. J Cardiothorac Vasc Anesth. 2015;29(1):95-100. 4. Crotti UA, Braile DM, Godoy MF, Murillo HG, Marchi CH, Chigutti MY, et al. Should the bidirectional Glenn operation be performed with or without cardiopulmonary bypass? Rev Bras Cir Cardiovasc. 2004;19(3):274-9. 5. LaPar DJ, Mery CM, Peeler BB, Kron IL, Gangemi JJ, et al. Short and long-term outcomes for bidirectional Glenn procedure performed with and without cardiopulmonary bypass. Ann Thorac Surg. 2012;94(1):164-70. 6. Fonseca L, Silva JP, Franchi SM, Castro RM, Comparato DO, Baumgratz JF. Bidirectional Glenn procedure in the staged treatment of hypoplastic left heart syndrome: early and late results. Braz J Cardiovasc Surg. 2005;20(1):1-7.

CONCLUSION

7. Fantini FA, Gontijo Filho B, Lopes RM, Castro MF, Barrientos A, Paula e Silva JA, et al. Bidirectional Glenn procedure: the importance of "pulsatile" flow in the pulmonary artery. Rev Bras Cir Cardiovasc. 1995;10(1):25-33.

This case report showed a really good evolution combining the off-pump bidirectional Glenn procedure with a right anterior thoracotomy approach. A larger series of patients is needed to evaluate the proper indications and results of this technique. In our service now we are selecting patients not previously operated, without adherences and without a BT shunt sutured in the right pulmonary artery, meanwhile the learning curve would overpassed. We consider this proposed technique as a good and safe option in a favorable patients avoiding median sternotomy and extracorporeal circulation with all of the related problems when possible achieving excellent results.

8. Glenn WW. Circulatory bypass of the right side of the heart. IV. Shunt between superior vena cava and distal right pulmonary artery: report of clinical application. N Engl J Med. 1958;259(3):117-20. 9. Tanoue Y, Kado H, Boku N, Tatewaki H, Nakano T, Fukae K, et al. Three hundred and thirty-three experiences with the bidirectional Glenn procedure in a single institute. Interact Cardiovasc Thorac Surg. 2007;6(1):97-10. 10. Hussain ST, Bhan A, Sapra S, Juneja R, Das S, Sharma S. The bidirectional cavopulmonary (Glenn) shunt without cardiopulmonary bypass: is it a safe option? Interact Cardiovasc Thorac Surg. 2007;6(1):77-82.

Authors’ roles & responsibilities MG ALC GG GG EG MV FP MP

Conception and design; manuscript writing or critical review of its content Manuscript writing or critical review of its content Conception and design; manuscript writing or critical review of its content Manuscript writing and critical review of its content Conception and design Manuscript writing and critical review of its content Conception and design Conduct of operations and experiments

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Cardoso CC, et al. - Pediculated myxoma from atrial septum invading atria CLINICAL-SURGICAL CORRELATION and biventricular inlets

Pediculated myxoma from atrial septum invading atria and biventricular inlets Mixoma pediculado do septo interatrial invadindo átrios e vias de entradas biventriculares

Camila Caetano Cardoso1, MD; Ulisses Alexandre Croti1, MD, PhD; Carlos Henrique De Marchi1, MD; Airton Camacho Moscardini1, MD DOI: 10.5935/1678-9741.20150048

RBCCV 44205-1671

Descriptors: Myxoma. Heart Murmurs. Dyspnea.

Descritores: Mixoma. Sopros Cardíacos. Dispneia.

CLINICAL DATA

+ 30° and PR interval of 0.12 s. Overload in both atria without ventricular overload. Ventricular repolarization unchanged.

A 7 years and 10 months old male child, 25 kg, born and raised in São José do Rio Preto, SP, referred for heart murmur and fatigue investigation. Dyspneic for three months and progressive worsening associated to sporadic dorsal region pain upon moderate exertion. Three days earlier he presented postprandial vomiting, loss of appetite and worsening of general condition. Upon physical examination the patient was in regular state: pale, hydrated, eupneic and afebrile. Regular heart rhythm with systolic murmur 4 + / 6 + and tachycardia. Clear lung sounds. Distended and painful abdomen upon palpation, along with hepatomegaly (liver palpable at 2.36 inches from the right costal margin). Blood pressure and heart rate were normal in all four limbs and without edema.

RADIOGRAPHY Visceral situs solitus in levocardia. Increased cardiac area with a cardiothoracic index of 0.65 and pulmonary vasculature within normal limits. ECHOCARDIOGRAM Situs solitus in levocardia, all connections were concordant. Significant dilation of both atria with moderate mitral valve regurgitation and important tricuspid valve regurgitation. Moderate pericardial effusion. Presence of large pediculated, lobed and homogeneous mass originating from the atrial septum occupying both right and left atria and projecting into the biventricular inlet tract during diastole, causing blood flow obstruction. Normal ejection fraction (Figures 1A and 1B).

ELECTROCARDIOGRAM Sinus rhythm with a heart rate of 122 beats/min, QRS axis

Watch the video acessing the link below: http://www.rbccv.org.br/video/2423/Pediculated-myxoma-from-atrial-septum-invading-atria-and-biventricular-inlets Serviço de Cardiologia e Cirurgia Cardiovascular Pediátrica de São José do Rio Preto - Hospital da Criança e Maternidade de São José do Rio Preto and Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil.

Correspondence Address: Ulisses Alexandre Croti Hospital de Base Faculdade de Medicina de São José do Rio Preto (FAMERP) Avenida Brigadeiro Faria Lima, 5544 - São José do Rio Preto, Brazil Zip code: 15090-000 E-mail: uacroti@uol.com.br

1

This study was carried out at Serviço de Cardiologia e Cirurgia Cardiovascular Pediátrica de São José do Rio Preto - Hospital da Criança e Maternidade de São José do Rio Preto - Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil.

Article received on June 11th, 2015 Article accepted on July 5th, 2015

No financial support

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The suggestive clinical status of low cardiac output, altered cardiac auscultation and the presence of two intracardiac tumor mass on echocardiography were fundamental for the diagnosis and surgical resection indication[1,2]. The radiological exam used for this diagnosis was the echocardiogram because it is a non-invasive exam and has an excellent sensitive. The histologic diagnosis was confirmed by pathological examination after operation, as it is shown in Figure 2[3,4].

Abbreviations, acronyms & symbols CPB

Cardiopulmonary bypass

A

B

Fig. 2 - Microscopically round, polygonal, or stellate cells are seen surrounded by abundant loose stroma rich in acid mucopolysaccharides. Myxoid stroma with recent and late hemorrhagic areas with hemosiderin pigments. OPERATION Median sternotomy found a greatly increased right atrium. Heparinization at 4mg/kg and careful aorta and vena cava cannulation were performed to avoid embolization. Cardiopulmonary bypass (CPB) was initiated, antegrade blood cardioplegia, hypothermic at 39°F and intermittent every 20 minutes. Right atrium was opened and large gelatinous mass was found, darkened and ocher colored. It was pulled gently releasing the entire right ventricular inlet and noting that there was no adhesion of the mass to the right atrial or ventricular walls, just fixed to the atrial septum. It was opted for resection of the atrial septum since the additional tests showed presence of mass also occluding the left side. After opening the atrial septum it was observed that the tumor obstructing both sides originated from the same site. The atrial septum was completely resected along with the tumor, which also showed no adhesions in the left cavities, subsequently reconstructed with bovine Braile BiomÊdicaŽ pericardial patch in a conventional way (Figures 3A, 3B and 3C).

Fig. 1 - A. Two-dimensional echocardiogram preoperatively showing the masses within the atria. The largest mass is located in the right atrium and occupies all of its cavity. It measures 2.75 x 1.57 inches in its greatest diameter. The mass in the left atrium measuring 1.77 x 1.18 inches; B. Invagination of the masses to the ventricles interior during diastole. DIAGNOSIS Myxomas represent around half of all heart tumors and may be associated with dominant family autosomal syndromes. The majority of them affects the left atrium, but can be present in other sites. The main differential diagnosis is rhabdomyoma[1].

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A

The CPB time was of 50 minutes and myocardial ischemia of 34 minutes at 93ºF. The postoperative period was uneventful with hospital discharge after six days of hospitalization. ACKNOWLEDGMENT To our Nurse Educator Bruna Cury from Hospital da Criança e Maternidade de São José do Rio Preto, SP for her collaboration in elaborating this text into the English language.

B Authors’ roles & responsibilities CCC UAC

CHDM

C

ACM

Analysis and/or data interpretation; conception and design study; final manuscript approval; manuscript writing or critical review of its content Analysis and/or data interpretation; conception and design study; final manuscript approval; manuscript writing or critical review of its content; realization of operations and/or trials; statistical analysis Analysis and/or data interpretation; conception and design study; final manuscript approval; manuscript writing or critical review of its content Analysis and/or data interpretation; conception and design study; final manuscript approval

REFERENCES 1. Beroukhim RS, Prakash A, Buechel ER, Cava JR, Dorfman AL, Festa P, et al. Characterization of cardiac tumors in children by cardiovascular magnetic resonance imaging: a multicenter experience. J Am Coll Cardiol. 2011;58(10):1044-54. 2. Padalino MA, Vida VL, Boccuzzo G, Tonello M, Sarris GE, Berggren H, et al. Surgery for primary cardiac tumors in children: early and late results in a multicenter European Congenital Heart Surgeons Association study. Circulation. 2012;126(1):22-30.

Fig. 3 - A. Pediculated tumor in the atrial septum (arrow) removed from right atrium and right ventricular inlet. Note that there was no adhesion to the cavities; B. Atrial septum resected with the pediculated tumor and obstructing the left atrium and the left ventricle inlet. The arrow indicates the remnants of the tumor to the right of the atrial septum featuring both cavities affected by the same mass; C. Resected tumor diameters to the left (a) and to the right (b). In the atrial septal remnant (arrow) can be observed the presence of the tumor witch occupied the right and left atria.

3. Pinede L, Duhaut P, Loire R. Clinical presentation of left atrial cardiac myxoma. A series of 112 consecutive cases. Medicine (Baltimore). 2001;80(3):159-72. 4. Croti UA, Braile DM, Souza AS, Cury PM. Right ventricle and tricuspid valve myxoma. Rev Bras Cir Cardiovasc. 2008;23(1):142-4.

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Letters to the Editor

Letters to the Editor DOI: 10.5935/1678-9741.20150063

RBCCV 44205-1672

Relationship between pre-extubation positive endexpiratory pressure and oxygenation after coronary artery bypass grafting

that there are several items of CONSORT Statement that have been omitted, such as calculating the number of patients in each group; the kind of randomization method that was chosen; the critical analysis of the external validity of the work as well as the discussion of the study limitations. These observations are consistent with Hopewell et al.[9] findings since they once have reported the conclusion in scientific magazines, CONSORT Statement is included for instructions to authors, there are more items of the Checklist in each clinical trial than in those in which this method is not mentioned. Randomized clinical trials are reliable sources of scientific information; however, the use of inappropriate methodology can lead to false conclusions, undermining the reliability of the study. Thus, the implementation of this methodology helps editors to assess trial quality and assures readers the reliability of conclusions reported at the end of each paper. It is our role, as reviewers and editors of the Brazilian Journal of Cardiovascular Surgery, to encourage authors to use the CONSORT Statement not only to facilitate the certification process of the study’s conclusions, but also in order to increase the quality of their own manuscripts.

At least one methodological error can be found in most randomized clinical trials that have been published in scientific journals; that is, some authors make such error compromising the reliability of the entire study. Some studies not even show the data in a systematic way; in consequence, even the best reviewers are not able to certify the results[1]. To provide a more reliable and easily certified content by the reviewers, a selected group of researchers, methodologists, statisticians and scientific journal editors have met to create a set of guidelines in a Checklist format[2,3]. “Consolidated Standards for Reporting Trials” was the generic name given for such guidelines or CONSORT Statement as it is known. In 1996[4], the first version was published, under some changes until 2010[2]; remaining this as the current version. This set of rules was initially designed to guide randomized clinical trials; being inappropriate for surgical work, in which there is greater difficulty in applying the blind condition for patients and evaluators to minimize either variations in surgical techniques as differences on the surgeons’ experience who perform these procedures[5]. For this purpose, it was published an extension of the CONSORT Statement in 2008 that provided specific recommendations for reporting randomized trials for non-pharmacological treatment (CONSORT-NPT)[6,7]. For these non-pharmacological work, there are specific instructions for each section of the paper; such as the Title with the word “randomized”, Abstract with the blind condition of the study, Method calculating the minimum number of patients to be included in each group, flow-chart, among others. A full description of such rules can be found in Boutron et al.[6] work. The work entitled “Relationship between pre-extubation positive end-expiratory pressure and oxygenation after coronary artery bypass grafting” of Borges et al.[8] published in this issue of the Brazilian Journal of Cardiovascular Surgery includes some of these criteria. At first, the authors define the study as randomized in the Abstract; the Methodology shows clear inclusion and exclusion criteria presented in text format, detailed description of the Methods to be applied to patients according to their groups, detailed statistics and, in the Results, graphical flow-chart type of the number of patients in each study phase. We congratulate the authors for the effort of reporting such results obeying rules that help ensure a high standard of reliability in their study. Nevertheless, we should draw attention

Marcos Aurélio Barboza de Oliveira, PhD - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, São Paulo, Brazil; UNIFEV, Votuporanga, SP, Brazil; Antonio Carlos Brandi, PhD; Carlos Alberto dos Santos, PhD; Paulo Henrique Husseini Botelho, MD - Hospital de Base São José do Rio Preto, São José do Rio Preto, SP, Brazil.

REFERENCES 1. Turner L, Shamseer L, Altman DG, Schulz KF, Moher D. Does use of the CONSORT Statement impact the completeness of reporting of randomised controlled trials published in medical journals? A Cochrane review. Syst Rev. 2012;1:60. 2. CONSORT 2010. The Lancet. 2010;375(9721):1136. 3. Calvert M, Blazeby J, Altman DG, Revicki DA, Moher D, Brundage MD; CONSORT PRO Group. Reporting of patientreported outcomes in randomized trials: the CONSORT PRO extension. JAMA. 2013;309(8):814-22. 4. Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, et al. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA. 1996;276(8):637-9.

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5. Nagendran M, Harding D, Teo W, Camm C, Maruthappu M, McCulloch P, et al. Poor adherence of randomised trials in surgery to CONSORT guidelines for non-pharmacological treatments (NPT): a cross-sectional study. BMJ Open. 2013;3(12):e003898.

of an extension for trials assessing nonpharmacologic treatments. Ann Intern Med. 2008;148(4):W60-6. 8. Lima RO, Borges DL, Costa MDAG, Baldez TEP, Silva MGBE, Sousa FAS, et al. Relationship between pre-extubation positive endexpiratory pressure and oxygenation after coronary artery bypass grafting. Rev Bras Cir Cardiovasc. 2015;30(4):443-8.

6. Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P, CONSORT Group. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. 2008;148(4):295-309.

9. Hopewell S, Ravaud P, Baron G, Boutron I. Effect of editors' implementation of CONSORT guidelines on the reporting of abstracts in high impact medical journals: interrupted time series analysis. BMJ. 2012;344:e4178.

7. Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P, CONSORT Group. Methods and processes of the CONSORT Group: example

DOI: 10.5935/1678-9741.20150056

RBCCV 44205-1673

Key points of reducing neurologic complications in frozen elephant trunk technique

room, without the use of scopes or guidewire. How can authors identify the true lumen? Wasn’t it a risk? Can mentioned neurologic complications as well as renal failure be associated with possible selection of incorrect lumen? Why didn’t authors use guidewire? Has the dissection also included both femoral arteries? Hybrid operating room doesn’t exist in many centers, however, guidewire may be used to identify true lumen. In our center, we also don’t have hybrid operating room, but we routinely use guidewire from intact femoral artery through descending thoracic aorta in retrograde way. Therefore we are able to see the true lumen directly. In conclusion, we consider that, this single stage technique is so useful especially in complex aortic pathologies. Learning curve is a reality of these novel strategies of course, but morbidity rates can be decreased with appropriate surgical strategies and known guideline recommendations.

Dear editor, We have read the interesting article entitled “Surgical treatment of complex aneurysms and thoracic aortic dissections with the Frozen Elephant Trunk technique” carefully[1]. The authors report their initial experience with this technique in 21 patients. First of all we appreciated the authors for this nice study. We would like to add some critics about this study. There were some neurologic complications such as stroke (in one patient) and paraplegia (in two patients) in the study. Did the authors make any assessment about neurologic complications and their protection strategies? This is a very important point that should be detailed in paper. The exact mechanism of spinal cord injury in frozen elephant trunk interventions is not fully understood. Stent graft length, thromboembolism, and spinal cord ischemia time during total circulatory arrest are considered responsible factors[2]. Cerebrospinal fluid drainage is recommended for spinal cord protection strategy in current guideline (Class I, level of evidence B)[3]. Proximal aortic pressure maintenance and distal aortic perfusion are some of the other recommendations (Class IIa, level of evidence B). From this point, did the authors use any of suggested protection method? On the other hand, neurologic complications can also be associated with distal length of endovascular prosthesis. In literature, 130 mm stent length is recommended for preventing paraplegia[2]. What was the distal length of prosthesis in these patients? Did authors make any assessment about distal position of stent in patients with neurologic complications? The authors performed surgery in conventional operating

Murat Kadan, MD; Gokhan Erol, MD; Kubilay Karabacak, MD; Mevlüt Kobuk, MD; Gulhane Military Academy of Medicine, Etlik Ankara, Turkey.

REFERENCES 1. Dias RR, Duncan JA, Vianna DS, Faria LB, Fernandes F, Ramirez FJ, et al. Surgical treatment of complex aneurysms and thoracic aortic dissections with the Frozen Elephant Trunk technique. Rev Bras Cir Cardiovasc. 2015;30(2):205-10. 2. Jakob H, Tsagakis K, Pacini D, Di Bartolomeo R, Mestres C, Mohr F, et al. The International E-vita Open Registry: data sets of 274 patients. J Cardiovasc Surg (Torino). 2011;52(5):717-23.

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3. Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE Jr, et al.; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/ SIR/STS/SVM guidelines for the diagnosis and management

of patients with thoracic aortic disease: executive summary. A report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Catheter Cardiovasc Interv. 2010;76(2):E43-86.

DOI: 10.5935/1678-9741.20150057

RBCCV 44205-1674

Answer to “Key points of reducing neurologic complications in frozen elephant trunk technique”

end of the prosthesis so as not to harm the dissected layer of the aorta; and for chronic dissections with small true lumen, the pull back traction was also an issue and sometimes it would take several minutes to release the prosthesis. They have changed and now we no longer face this problem. The stent graft length is not an issue, in my opinion. None was longer than 15 centimeters. In addition, when doing total endovascular procedures, we have covered the entire descending aorta in many cases and we did not have paraplegia. Cerebral fluid drainage as a spinal cord protection strategy is regularly used, but not for these operations. If you do not have a proximal hypertension hemodynamic situation, which happens in these controlled proximal brain perfusions, there is no reason for cerebral fluid drainage (the situation is completely different from the thoracoabdominal aorta operations). In conclusion, we can say that with a better and faster surgical procedure, we can regularly do this operation in less than 60 minutes of body circulatory arrest time and no longer have these devastating complications. Yours sincerely, Ricardo Ribeiro Dias, Jose Augusto Duncan - Incor, USP – São Paulo, SP, Brazil

Dear Editor, We appreciated the comments of the colleagues regarding our role and we completely agree with the considerations related to the need of reducing morbidity. With this in mind, we can say that all points must be addressed in order to prevent morbidity and mortality in our patients. Recently, we started to operate on this type of surgery in a hybrid operating room, but in the beginning of the learning curve, we did not. Many years ago, when we first started placing stents in the descending aorta, in acute type B dissections, with a Brazilian short endovascular stent graft (9 cm length), which was very smooth and easy to handle, we learned how to do it without a guidewire, which is actually impossible with the current stent grafts. Nowadays, we use the guidewire in almost all cases. In the beginning of the “Evita Open” experience (the only stent graft available here in Brazil for the frozen elephant trunk procedure), the device had a soft but big “ball” at the

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REVIEWERS

Reviewers BJCVS 30.4 The Brazilian Journal of Cardiovascular Surgery (BJCVS), once again, is grateful for the reviewers, listed below. Their hard work has been fundamental to our journal publishes articles compatible with the requirement of our readers.

Alfredo Inácio Fiorelli

Lindemberg da Mota Silveira Filho Luciana da Fonseca da Silva Luiz Fernando Caneo

Bruno Botelho Pinheiro Diego Felipe Gaia

Marcos Aurélio Barboza de Oliveira Marcos Vinicius Pinto e Silva Marcus Vinicius Ferraz de Arruda (in memoriam)

Enio Buffolo Fabio Binhara Navarro Fernando Antoniali Fernando Ribeiro de Moraes Neto

Neuseli Martino Lamari Nilson Antunes Olívio Alves Souza Neto Orlando Petrucci Otoni Moreira Gomes

Guilherme Agreli Henrique Murad

Renata Gabaldi

João Galantier José Ernesto Succi José Glauco Lobo Filho

Vera Lúcia dos Santos Alves

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INFORMATION FOR AUTHORS BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY/ Revista Brasileira de Cirurgia Cardiovascular Editor-in-Chief Prof. Dr. Domingo M. Braile Av. Juscelino Kubitschek de Oliveira, 1.505 – Jardim Tarraf I 15091-450 – São José do Rio Preto – SP - Brasil E-mail: revista@sbccv.org.br

Electronic Submission Manuscripts should be compulsorily submitted electronically on site http://www.rbccv.org.br/sgp/. When entering this link, the system will ask for the username and password if the user have already registered. Otherwise, click on “I want to register” and register. Or, if the user have forgotten his password, the mechanism to remember the password can be used, which will generate an email containing such password. The submission system is self-explanatory and includes eight steps: Step 1: Classification of the article Step 2: Adding title and keywords Step 3: Registering for authors Step 4: Inclusion of summary and Abstract Step 5: Inclusion of the manuscript itself with references Step 6: Sending images Step 7: Generation of copyright declarations, conflict of interest and copy of the Opinion of the Research Ethics Committee of the Institution Step 8: Author’s approval / finalization of submission

The Brazilian Journal of Cardiovascular Surgery (BJCVS) is the official journal of the Brazilian Society of Cardiovascular Surgery (BSCVS). It is a bimonthly publication, with regular circulation since 1986. BJCVS is indexed in the Thomson Scientific (ISI), Medline/PubMed, SCOPUS, SciELO, LILACS, Scirus and SCImago database. BJCVS aims to record the scientific production in cardiovascular surgery, encouraging the study, improving and updating the professional specialty. Studies submitted for publication in BJCVS must deal with themes related to cardiovascular surgery and related fields. The journal publishes the following types of articles: original article, editorial, review article, special article, case report, how to do it, short communications, preliminary notes, clinical-surgical correlation, experimental study, multimedia and letter to editor. Acceptance will be based on originality, significance and scientific contribution. Articles with merely propaganda or commercial purposes will not be accepted. The authors are responsible for the content and information contained in their manuscripts. BJCVS vehemently rejects plagiarism and self-plagiarism. On submission of manuscripts, the authors sign a statement declaring they are aware of the consequences of violation.

The texts must be edited in word format and figures and tables should be in separate files. Keep your records updated because communication with authors is exclusively by e-mail. When finishing the submission of the study, it will generate an e-mail stating that the submission was made correctly, another email will be generated after checking if it is within the standards. If the article is “Out of Standard”, the author will be notified by email and can fix it into the SGP / BJCVS in www. bjcvs.org/sgp. Authors may follow the course of their study at any time by SGP/BJCVS through the flow code automatically generated by GSP, or even by the title of his study.

The journal will be published in full on the journal’s website (www.rbccv.org.br/www.bjcvs.org) and SciELO (www. scielo.br/rbbcv), with specific links in the BJCVS site (www. sbccv. org.br) and CTSnet (www.ctsnet.org). EDITORIAL POLICY Standard BJCVS adopts the Standards of Vancouver - Uniform Requirements for Manuscripts Submitted to Biomedical Journals, organized by the International Committee of Medical Journal Editors, available at: www.icmje.org Submission and Publication Policy Only manuscripts whose data is not being assessed by other journals and/or have not been previously published will be considered for review. Manuscripts accepted may only be reproduced in whole or in part, without the express consent of the editor of BJCVS.

Peer review All scientific contributions are reviewed by the Editor, Associate Editors, Editorial Board Members and/or Guests Reviewers. The reviewers answer a questionnaire in which they rated the manuscript, their rigorous examination on all items that compose a scientific study by assigning a score for each of the questionnaire items. At the end, general comments about the study and suggestion if it should be published, cor-

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rected according to the recommendations or definitively rejected are made. With these data, the Editor will make a decision. In case of discrepancies between the reviewers, a new opinion can be requested in order to provide a best judgment. When modifications are suggested, they will be forwarded to the author and then the reviewers to verify that these requirements have been met. The authors have 30 days to make the changes requested by reviewers and resubmit the article. In response to the comments/suggestions of the reviewers, authors should highlight the changes made in the text. The non-observance of this period will involve the removal of the article from the review process. Once the article is approved, authors will be notified by e-mail registered on the site and shall forward an abstract of up to 60 words in Portuguese and English, of the article. They are inserted into the electronic mailing and sent to all members when the BJCVS is available online. Once accepted for publication, a proof of the edited article (PDF format) will be sent to the corresponding author for assessment and final approval.

criteria established by WHO and ICMJE, whose addresses are available at the ICMJE website (http:// www.icmje.org/). The number should be recorded at the end of the abstract. The statement of approval of the study by the Ethics and/ or Scientific Institutional Committee must be sent at the time of submission of the manuscript. Copyright Transfer and Declaration of Conflict of Interest The authors should submit manuscripts at the time of submission, the copyright declaration signed by all authors. All published manuscripts become the permanent property of the Brazilian Journal of Cardiovascular Surgery and can not be published without the written consent of the editor. Likewise, for confirmation of the submission of the manuscript a statement of conflict of interest, signed by all authors should be sent. Both documents, statement of copyright transfer and declaration of conflicts of interest, are standardized and generated by the SGP at the time of submission of the manuscript. Authoring Criteria & Individual Contribution to Research We suggest the author to adopt the criteria for authorship of the articles according to the recommendations of the International Committee of Medical Journal Editors. Thus, only those people who contributed directly to the intellectual content of the study should be listed as authors. Authors should meet all the following criteria in order to be able to take public responsibility for the content of the study: 1. have conceived and planned the activities that led to the study or interpreted the data it presents, or both; 2. have written the study or revised successive versions and took part in the review process; 3. have approved the final version.

Language Articles should be written in English, using easily and accurately language and avoiding informality of colloquial language. For those studies whose standard the English language is deemed inappropriate by the Editorial Board, the journal will provide correction and costs should be assumed by the authors. Ethical Issues Research on human subjects must be submitted to the Ethics Committee of the institution, fulfilling the Declaration of Helsinki 1975, revised in 2008 (World Medical Association, available at: http://www.wma.net/en/30publications/10policies/b3/ 17c.pdf) and Resolution 196/96 of the National Health Council (available at: http://conselho.saude. gov.br/resolucoes/reso_96.htm). In experimental study involving animals the guidelines established in the Guide for Care and Use of Laboratory Animals should be respected (Institute of Laboratory Animal Resources, National Academy of Sciences, Washington, DC, United States), 1996, and Ethical Principles Animal Experimentation (Brazilian College of Animal Experimentation COBEA, available at: www.cobea.org.br), 1991. Randomized studies should follow the CONSORT guidelines (available at: www.consort-statement.org/consort-statement). BJCVS supports policies for the registration of clinical trials of the World Health Organization (WHO) and the International Committee of Medical Journal Editors (ICMJE), recognizing the importance of these initiatives for the registration and international open access dissemination of information on clinical trials. Thus, only be accepted for publication, the clinical research articles that have received an identification number in one of the Clinical Trial Registers validated by the

People who do not meet the above requirements and who had purely technical or of general support participation, should be mentioned in the acknowledgments section. On submission, the kind of contribution of each author when performing the study and manuscript preparation in the following areas should be made explicit: 1. Study Design 2. Collection, analysis and interpretation of data 3. Drafting of the manuscript Abbreviations and Terminology The use of abbreviations should be minimal. When extensive expressions need to be repeated, it is recommended that their initial capital letters replace them after the first mention. It should be followed by the letters in parentheses. All abbreviations in tables and figures should be defined in the respective legends. The use of abbreviations in the Summary and Abstract Should be avoided.

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Only the generic name of the drug used should be cited in the study, and we discourage the use of trade names. BJCVS adopts Universal Official Anatomical Terminology, approved by the International Federation of Anatomists Associations (FIAA).

by the International Committee of Medical Journal Editors (ICMJE, available at: http://www.icmje.org). References should be identified in the text with Arabic numerals in square brackets, following the order of citation in the text, overwritten. The accuracy of references is the responsibility of the author. If more than two references were cited in sequence, only the first and last must be typed, separated by a dash (Example: [6-9]). In case of alternate citation, all references should be typed, separated by commas (Example: [6,7,9]). Publications with up to six authors, all authors should be cited; publications with more than six authors, the first 6 followed by the Latin phrase “et al.” should be cited. Titles of journals should be abbreviated according to the List of Journals Indexed for MEDLINE (available at: http:// www.nlm.gov/tsd/serials/lji.html).

PREPARATION OF MANUSCRIPT Manuscript Sections Title and Authors. The study title, in Portuguese and English, should be concise and informative. The full names of authors, titles and their institutional affiliation should be provided. Summary and Abstract. The abstract should be structured in four sections: Objective, Methods, Results and Conclusion. The Abstract (literal version, in English, of Abstract in Portuguese) should follow the same structure of the summary into four sections: Objective, Methods, Results and Conclusion. Abbreviations should be avoided. The maximum number of words should follow the recommendations in the table. In the Articles Case Reports and How-I-Do, the abstract should not be structured (informative or free). The Clinical and Surgical Correlations and sections Multimedia exempt summary and abstract. Descriptors: From three to five descriptors (keywords) should also be included as well as their translation. The descriptors can be found at the website http://decs.bvs.br/, which contains terms in Portuguese, Spanish and English or www.nlm.nih.gov/mesh for terms in English only, or in the respective links available at the submission system of the journal. Body of the manuscript. Original Articles and Experimental Study should be divided into the following sections: Introduction, Methods, Results, Discussion, Conclusion and Acknowledgements (optional). The Case Reports should be structured in sections: Introduction, Case Report and Discussion, and Clinical-surgical Correlations in Clinical Data, Electrocardiography, Radiogram, Echocardiogram, Diagnosis and Operation. The section Multimedia should have the following sections: Patient Characterization and Description of the Technique. The Review Articles and Special Articles can be structured into sections according the author’s criteria. Letters to the Editor, in principle, should comment, discuss or criticize articles published in BJCVS, but it can also be about other topics of general interest. It is recommended a maximum size of 1000 words, including references - that should not exceed five, and they may or may not include title. Whenever possible and appropriate, a response from the authors of the article in question will be published with the letter.

References Models Journal Article Issa M, Avezum A, Dantas DC, Almeida AFS, Souza LCB, Sousa AGMR. Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta. Rev Bras Cir Cardiovasc. 2013;28(1):10-21. Organization as Author Diabetes Prevention Program Research Group. Hypertension, insulin, and proinsulin in participants with impaired glucose tolerance. Hypertension. 2002;40(5):679-86. No indication of authorship 21st century heart solution may have a sting in the tail. BMJ. 2002;325(7357):184. Article electronically published before the print version (“ahead of print”) Atluri P, Goldstone AB, Fairman AS, Macarthur JW, Shudo Y, Cohen JE, et al. Predicting right ventricular failure in the modern, continuous flow left ventricular assist device era. Ann Thorac Surg. 2013 Jun 21. [Epub ahead of print] Online Journal Article Machado MN, Nakazone MA, Murad-Junior JA, Maia LN. Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center. Rev Bras Cir Cardiovasc [online]. 2013[cited 2013 Jun 25];28(1):29-35. Available from: <http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-76382013000100006&lng=en&nrm=iso> Book Chapter Chai PJ. Intraoperative myocardial protection. In: Mavroudis C, Backer C, eds. Pediatric cardiac surgery. 4th ed. Chichester: Wiley-Blackwell; 2013. p.214-24.

References The references of the print and electronic records must be standardized according to the Vancouver standard, prepared

Book Cohn LH. Cardiac surgery in the adult. 4th ed. New York: McGraw-Hill;2012. p.1472.

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Thesis Dalva M. Estudo do remodelamento ventricular e dos anéis valvares na cardiomiopatia dilatada: avaliação anátomo-patológica [Tese de doutorado]. São Paulo: Universidade de São Paulo, 2011. 101p.

alphabetically at the bottom, with their forms in full. Likewise, the abbreviations employed in the figures should be explained in the legends. The figures will be published in color only if the author agrees to bear the cost of printing color pages. We will only accept images in TIFF or JPEG format with a minimum resolution according to the type of image, both for black and white and for color images. BJCVS prompts the authors to archive their possession the original images, as if the images submitted online present any impediment to print, we will contact the author to send us these originals.

Legislation Conselho Nacional de Saúde. Resolução n. 196, de 10 de outubro de 1996. Dispõe sobre diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Bioética. 1996;4(2 Supl):15-25. Other examples of references can be found at: http://www.nlm.nih.gov/bsd/uniform_requirements.html

Limits by Type of Article Aiming at streamlining the space of the journal and allow a higher number of articles per issue, the criteria below outlined should be met according the type of publication. The electronic counting of words should include the home page, abstract, text, references, and figure legends. The titles have a maximum of 100 characters (counting spaces) for Original Articles, Review and Update Articles and Experimental Study and 80 characters (counting spaces) for the other categories.

Tables and Figures Tables and Figures should be numbered according to the order of appearance in the text, with a title and be in separate files. Tables should not contain redundant data already cited in the text. They should be open on the sides and a totally white background. The abbreviations used in the tables should be listed

Table example: Cardiovascular Risk Factors in Study Group Cardiovascular Risk Factors Hypertension (>140 mm Hg systolic and >90 mm Hg diastolic) Insulin-dependent diabetes mellitus Hypercholesterolemy ( 240 mg/dL) Hypertriglyceridemy ( 250 mg/dL) Cigarette smoking ( 10 cigarettes/d) Previous contraceptive therapy Previous myocardial infarction Family history of cardiovascular disease

Figure example

Number of Patients 11 6 12 6 12 2 11 12

Percentage of Patients 55 30 60 30 60 10 55 60

Checklist before sending the manuscript - Submission letter indicating category of manuscript - Declaration from authors and co-authors saying that they agree with the content of manuscript - Research approved by the Institution Ethics Comitee - Manuscript made out in Word 2007 text processor or superior (format A4); type 12; space 1,5; font Times News Roman; paged

Histogram showing effects of transdermal 17ß-estradiol on left internal mammary artery (LIMA) graft cross-sectional area. It increased by 30% (3.45 ± 1. 2 mm2 versus 4.24 ± 1 mm2; p = 0.039).

- Manuscript within limits adopted by Brazilian Journal of Cardiovascular Surgery for its category

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Maximum number of authors Abstract maximum number of words Maximum number of words Maximum number of references Maximum number of figures and tables Running title

Letters to the Editor

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ClinicalSurgical Correlation

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Meetings Calendar

Braz J Cardiovasc Surg 2015;30(4):513-4

MEETINGS CALENDAR - 2015

September

18 to 21 - PICS~AICS 2015 Pediatric & Adult Interventional Cardiac Symposium Las Vegas, United States Informations: Kimberly Ray E-mail: kimberly_ray@pics-aics.com Site: http://www.picsymposium.com

3 to 6 – 3rd Heart Care Heart International Heart Symposium – Unite! For Better Heart Care Bangkok, Thailand Informations: Secretariat Phone: +662-591-8943, +6684-134-9898 E-mail: info@cdiheartdisease.org Site: http://www.cdiheartdisease.org

19 - PICS-AICS Symposium Joint Session with the Congenital Heart Surgeons – Building a Successful Hybrid Program – The Collaborative Approach Las Vegas, United States Informations: Ziyad M. Hijazi, MD Phone: 312-942-9524 Fax: 312-942-6801 E-mail: kimberly_ray@pics-aics.com Site: http://www.picsymposium.com

6 to 9 - VALVE 2015 – 7th Training Course for Minimally Invasive Valve Surgery Innsbruck, Austria Informations: Ms. Judith Kutnjak Phone: +43 1 867 49 44-21 Fax: +43 1 867 49 44-9 E-mail: judith.kutnjak@ee-hsec.org Site: http://www.focusvalve.org/index.php

19 and 20 - 14th Annual Symposium on Regional Anesthesia, Pain and Perioperative Medicine New York, United States Informations: Stacy Atkinson E-mail: stacy@nysora.com Site: http://www.nysorasymposium.com

8 and 9 - The 2nd International Surgical Aspects of Cardiopulmonary Transplantation Course Newcastle, United States Informations: Melissa O’Dwyer Phone: +44 (0) 114 225 9036 E-mail: melissa.odwyer@aesculap-academy.com

19 to 22 - 25th WSCTS World Congress Edinburgh, United Kingdom Informations: Phone: 0044 0131 527 1629 E-mail: info@wscts2015.org Site: www.wscts2015.org

9 and 10 - The 2nd International Surgical Aspects Newcastle, United Kingdom Informations: Melissa O’Dwyer E-mail: melissa.odwyer@aesculap-academy.com Site:https://uk.aesculap-academy.com/ go/?action=AkadEventData&event_id=411797&evdate=411801

24 to 26 - Duke Masters of Minimally Invasive Thoracic Surgery Conference Orlando, United States Informations: Patti Deshaies Phone: 919-681-6370 Fax: 919-668-4815 E-mail: patricia.deshaies@duke.edu

14 and 15 - Transcatheter Aortic and Mitral Valve Interventions Windsor, United Kingdom Informations: Sharon Pidgeon Phone: 01753 832166 Fax: 01753 620407 E-mail: sharon.pidgeon@eacts.co.uk

24 to 27 - JCTSE Educate the Educators (EtE) Course Rosemont, United States Informations: Rebecca J. Mark Phone: 312-202-5893 Fax: 312-202-5801 E-mail: rmark@jctse.org Site: http://www.jctse.org/whats-new/ete-2015-announcement/

14 and 15 – ESTS ‘Elancourt in Strasbourg’ - Maximally and Minimally Invasive Surgery - Tips and Tricks from the experts Strasbourg, France Informations: Yvonne Rice Phone: +44 1392 430671 Fax: +44 1392 430671 E-mail: admin@ests.org.uk Site: http://www.ests.org/education/ests_school/elancourt_ school.aspx

October

17 to 20 - Birmingham Review Course in Cardiothoracic Surgery Birmingham, United Kingdom Informations: L.R. Associates – Ms. L. Richardson Phone: 01296 733 823 Fax: 01296 733 823 E-mail: lorrainerichardson1@btinternet.com Site: www.birminghamreviewcourse.co.uk

2 and 3 - Advances in Thoracic Surgical Oncology New York, United States Informations: Phone: 646-227-2025 Fax: 212-557-0773 E-mail: cruzi1@mskcc.org, brodheap@mskcc.org Site: http://www.mskcc.org/thoracicsurgerycourse

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Meetings Calendar

Braz J Cardiovasc Surg 2015;30(4):513-4

3 to 7 - 29th EACTS Annual Meeting Amsterdam, Netherlands Informations: EACTS Phone: +44 (0)1753 832 166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk

Challenges and Complications Boston, United States Informations: American Association for Thoracic Surgery Phone: 978-927-8330 E-mail: meetings@aats.org Site: http://aats.org/Focus/

5 to 7 - 4th International Conference on Surgery 2015 Dubai, United Arab Emirates Informations: Isabella Jones E-mail: surgery@conferenceseries.com Site: http://surgery.conferenceseries.com/

27 to 30 – Congenital Heart Disease Windsor, United Kingdom Informations: EACTS Phone: +44 (0)1753 832 166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk Site: http://www.eacts.org/academy/2015-programme/

14 to 17 - ECTSS 2015 Annual Meeting Palm Beach, United States Informations: Scott Gerard or Brian Mozelak (for CME) Phone: 646-797-5292 E-mail: sgerard@ectss.org Site: http://www.ectss.org/2015meeting

30 and 31 - NWAC Subspecialty Series: Cardiac Anesthesia and Intensive Care Abu Dhabi, United Arab Emirates Informations: Pat Pokorny E-mail: pat@visionexpo.co Site: http://www.nwac.org/satellites

23 and 24 – AATS Focus on Thoracic Surgery: Technical

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BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

In 2016, the Brazilian Journal of Cardiovascular Surgery will celebrate 30 years of uninterrupted circulation. We will have many new features for our readers and contributors. ournal of lian J Ca azi

BJCVS

YEARS 1986 - 2016

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3O Br

Coming soon!!!



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