20.4.09

Beta-bloqueadores no perioperatório de intervenções cirúrgicas não cardíacas – os novos dados do estudo POISE

No dia 13 de maio a revista britânica The Lancet publicou, em seu site os resultados do estudo POISE e com isso iniciou um intenso debate que envolveu médicos, repórteres e pacientes. O estudo POISE é, até agora, o maior estudo clínico já realizado para investigar o papel dos beta-bloqueadores no perioperatório de intervenções cirúrgica não-cardíacas. Os mais de 8.000 indivíduos incluídos foram aleatorizados para receber metoprolol ou placebo. É importante salientar que somente as intervenções cirúrgicas eletivas foram analisadas e pacientes que já faziam uso de beta-bloqueador por outras razões, não foram incluídos neste estudo. Com relação aos desfechos cardiovasculares, como morte cardíaca e infarto não fatal, o POISE revelou resultados semelhantes aos estudos anteriores com menos pacientes: o grupo que recebeu metoprolol apresentou incidência de complicações significativamente menor do que o grupo controle. Por outro lado, o que chamou a atenção dos investigadores foi o resultado da análise dos desfechos secundários, morte por todas as causas e acidente vascular cerebral (AVC). Nesta análise, os pacientes que receberam metoprolol apresentaram taxas maiores de complicações. Segundo os autores, a hipotensão e a bradicardia, mais frequentes no grupo que recebeu metoprolol, teriam sido responsáveis pela maior ocorrência de complicações, em especial AVC. A interpretação desses dados fez os investigadores do POISE concluírem que o uso de metoprolol no ambiente perioperatório é capaz de reduzir a chance de complicações cardiovasculares, MAS a um custo muito elevado: aumento da chance de morte ou de AVC. Os autores do trabalho acrescentaram que as recomendações relativas ao uso de beta-bloqueadores contidas nas diretrizes de tratamento perioperatório deveriam ser reformuladas. O editorial que acompanha o artigo recomenda, entretanto, cautela com relação a esta decisão. Aponta problemas com relação à escolha da dose de metoprolol adotada pelo estudo POISE (100 mg na primeira dose, atingindo 200 mg por dia) ou seja, 50% da dose máxima permitida para esse medicamento. Segundo o editorial, esta dose é muito mais alta do que a utilizada em estudos anteriores, o que poderia explicar a ocorrência de hipotensão e bradicardia. De fato, a análise dos dados do POISE, incluindo o material adicional oferecido pelos autores e disponível no site da revista, revela que não foi desprezível o número de pacientes que desenvolveu hipotensão e bradicardia. Hipotensão e bradicardia, embora possam representar complicações potencialmente graves, quando prontamente reconhecidas e tratadas por meio de suspensão do beta-bloqueador e medidas para elevação da freqüência cardíaca e da pressão arterial, não estão associadas a elevações significativas de taxas de complicações. Estas conclusões provêm de estudos com pacientes na fase aguda do infarto agudo do miocárdio onde os beta-bloqueadores têm seu benefício comprovado, mesmo numa situação onde a hipotensão e bradicardia poderiam reduzir perfusão coronariana e aumentar o tamanho do infarto. Como lidar então com as informações do POISE aparentemente contraditórias aos conceitos arraigados e, mais importante, em conflito com a fisiopatologia das complicações cardiovasculares e com os mecanismos de cardio-proteção dos beta-bloqueadores? Mais uma vez, com cautela. Aqui vão algumas recomendações:

1. Os indivíduos em uso prévio de beta-bloqueador não foram incluídos no POISE. Este indivíduos NÃO devem ter o beta-bloqueador suspenso antes de intervenção cirúrgica não cardíaca.

2. TODOS os indivíduos que fazem uso de beta-bloqueadores no perioperatório de intervenções cirúrgicas não cardíacas devem ser rigorosamente monitorizados com relação à ocorrência de hipotensão e bradicardia. Caso uma destas complicações seja diagnosticada, o medicamento deve ser prontamente suspenso e devem ser estabelecidas medidas para sua correção.

3. Enquanto aguardamos análise mais detalhada dos dados do estudo POISE, recém publicado, as recomendações relativas ao uso de beta-bloqueadores no perioperatório de intervenções cirúrgicas não cardíacas devem ser mantidas.

Bruno Caramelli
Daniela Calderaro
Pai Ching Yu
Danielle Menosi Gualandro
Andre Coelho Marques

17.3.09

Alteração no perfil de coagulação e incidência de TVP em colecistectomia laparoscópica

Embora a colecistectomia laparoscópica parecer ser menos traumática aos pacientes, comparada à cirurgia aberta, a diminuição do retorno venoso dos membros inferiores e a hipercoagulabilidade que ocorre em pacientes submetidos à colecistectomia laparoscópica eletiva com pneumoperitônio por CO2 torna-se um fator de risco potente para a ocorrência de trombose venosa profunda (TVP).

 

Pesquisadores publicaram, recentemente, no International Journal of Surgery, um estudo observacional de 50 pacientes submetidos à colecistectomia laparoscópica eletiva, desenhado para avaliar alterações de TP, TTPa, D-dímero e antitrombina III, que foram medidos no pré-operatório, 6h e 24h após a cirurgia. Os pacientes foram acompanhados por ultrassom colorido duplex dos membros inferiores bilateralmente e no 7º pós-operatório para procurar por evidências de TVP.

 

Diminuição significativa pós-operatória de TTPa e de antitrombina III sugeriram ativação da coagulação, enquanto que a diminuição do D-dímero sugeriu ativação da fibrinólise. Valores de TP não apresentaram alterações estatisticamente significativas pós-operatórias. Idade, índice de massa corpórea e duração do pneumoperitônio correlacionaram-se à ativação significativa da coagulação e da fibrinólise. Nenhum paciente desenvolveu evidências clínicas ou radiológicas de TVP no período pós-operatório.

 

Os pesquisadores concluíram que o pneumoperitônio por CO2 aumenta a ativação da coagulação e da fibrinólise associadas à colecistectomia laparoscópica. Pacientes com fatores de risco como idade avançada, obesidade ou com expectativa de longa duração de cirurgia laparoscópica tendem a ter ativação significativa da coagulação, tornando-os um grupo de risco vulnerável ao desenvolvimento de TVP no pós-operatório, justificando a utilização de alguma forma de tromboprofilaxia.



Uma resenha de Alteration in coagulation profile and incidence of DVT in laparoscopic cholecystectomy - International Journal of Surgery; 2008 Dec 25. [Epub ahead of print]


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2.2.09

Antibiotic Prophylaxis Against Infective Endocarditis: New Guidelines, New Controversy?

Richard G. Bogle; Abhay Bajpai

Br J Cardiol.  2008;15(6):279-280.  ©2008 Medinews (Cardiology) Limited
Posted 01/12/2009
Introduction

For over 50 years cardiologists have routinely recommended antibiotic prophylaxis (ABP) at the time of dental procedures in patients deemed to be at risk of infective endocarditis (IE). Reviews and editorials all acknowledged the lack of robust evidence for effectiveness of ABP and from time to time the literature has been reviewed and expert opinion synthesised into guidelines. In the UK, the 2004 Joint Royal College of Physicians/British Cardiac Society guideline has been widely followed.[1] In 2006 new guidelines were published by the British Society for Antimicrobial Chemotherapy (BSAC).[2] These guidelines were important because this committee's recommendations are incorporated into the British National Formulary. The BSAC guidelines recommended withdrawal of ABP for the majority of patients limiting them to individuals perceived to be at the highest risk of IE (e.g. a prior history of IE, prosthetic cardiac valves and surgically constructed pulmonary or system shunts/conduits). These guidelines were welcomed by the majority of dentists and microbiologists as a step in the right direction. However, many cardiologists, who had seen first-hand the horrors of IE, did not wish to see the rejection of a therapy that was thought by most to be effective and harmless. The lack of agreement between the medical and dental professions resulted in the issue being referred to the National Institute for Health and Clinical Excellence (NICE) for an authoritative statement.[3]

NICE Guidance

The NICE review tried to determine which cardiac conditions are associated with increased risk of IE; whether dental treatment is associated with acute risk of developing the condition and whether ABP was effective in prevention of cases and deaths. The NICE guideline concluded that patients with structural heart disease were at increased risk of IE but did not find convincing evidence that dental ABP was cost-effective. They calculated that if amoxicillin prophylaxis was effective then the cost of preventing a single case of IE would be circa £12 million. In the absence of high-quality evidence for clinical effectiveness they recommended that routine dental ABP should be abandoned. The methodology employed by NICE was robust and transparent, in contrast to the evidence supporting ABP. The NICE guidelines development group usually review therapies supported by data from mega-trials and meta-analyses, however, the literature on ABP is more like the Dead Sea scrolls - fragmented, imperfect, subject to various interpretations and mainly missing. In this situation there is a strong reliance on expert opinion and many would agree that absence of evidence should not be regarded as evidence of absence. The poor quality of the supportive data and reliance on expert opinion probably explains the differences between the BSAC and American Heart Association/American College of Cardiology (AHA/ACC) guidelines and those of NICE. The NICE guideline development process is transparent and the comments from stakeholders are published. Review of these comments shows that the dental community is generally in favour of the new recommendations, which reinforce the link between good overall dental hygiene and prevention of IE rather than relying on ABP just at the time of dental work. Other stakeholders are concerned not only with the guideline itself but potential difficulties with implementation. In this respect the Department of Health stated that the guidelines were a "very significant shift in current clinical practice... we feel there is a serious risk of confusion and lack of compliance".

Reaction

The reaction to these guidelines has been predictable. Many cardiologists see them as a step too far and question the credibility of a guideline that is based around the reevaluation of weak historical evidence rather than high-quality clinical trials. To many cardiologists the case supporting ABP is simple: IE is a very serious disease with a high mortality and morbidity; decades of clinical experience have illustrated that certain patients are at increased risk; dental work is associated with bacteriaemia and antibiotics kill bacteria cheaply, effectively and with low toxicity. Most cardiologists acknowledge the lack of definitive evidence for effectiveness but believe that even if ABP prevents only a minority of IE, surely this is preferable. It is for these reasons we believe that most cardiologist are uneasy about the new guidelines. Of course we may never be able to measure the precise effectiveness of ABP and this uncertainty was acknowledged more than 25 years ago by Celia Oakley and Walter Somerville who hypothesised at least four reasons why ABP might fail:[4]

  • Perhaps it was not given.

  • Perhaps it was not given to the right people.

  • Perhaps it does not work.

  • Perhaps it is irrelevant.

Now that the guideline has been published various scenarios and difficulties may be envisaged. For example, if a cardiologist continues to recommend ABP for a patient but the dentist wants to follow the NICE guidelines. Each clinician has a separate duty of care to the patient and both may feel they are acting within the patient's best interest. While the view expressed by the cardiologist is a valid consideration, legally it is not definitive and would only be taken as part of the overall 'mix' of information. The Dental Protection organisation has already advised their members that if a cardiologist continues to recommend ABP it is inadvisable, as it conflicts with guidelines issued by an authoritative body; this recommendation holds even if it has been confirmed in writing by the cardiologist.[5]

The Art of Medicine

A survey of cardiologists, prior to the publication of the NICE guidelines, showed that 94% felt that patients with moderate risk of IE should receive ABP and 96% believed that it was unsafe not to recommend ABP to such patients prior to dental treatment.[6] With such overwhelming support for the status quo what is the legal position of the cardiologist who decides to act against the guideline? The Bolam defence stated that a doctor is not guilty of negligence if "he has acted in accordance with a practice accepted as proper by a responsible body of medical men skilled in that particular art".[7] Since NICE is a national body appointed by statute it is likely to be regarded as a responsible body. Although NICE guidelines are not enforceable in law the threat of legal action might lead cardiologists, while not agreeing with the guidelines, to comply with them since any potential legal action could be robustly defended. However, compliance with guidelines due to a fear of litigation could, in time, weaken the Bolam defence due to a lack of variation in practice. Over 2,000 years ago, Plato explored the difference between skills grounded in practical expertise and those based solely on following instructions or obeying rules. He argued that once the medical profession dedicates itself to the provision of healthcare through guidelines it is committed to continue observing them because, at that point, the expertise resides within the guidelines rather than the clinician. Once this occurs then any guideline deviation is unjustifiable on the basis of clinical judgement.

In clinical cardiology we are used to facing decisions where the clinical evidence base does not completely apply to the particular patient at hand. In this situation we give an opinion - a belief based not on positive knowledge but on what seems valid, true, or probable to one's own mind. It is time for cardiologists to do that with ABP. If we believe, as a group, that NICE has gone too far in recommending the abolition of ABP then we should act together as a responsible body of doctors robustly defending the Bolam principle and our right to clinical judgement

References

  1. Ramsdale DR, Turner-Stokes L. Prophylaxis and treatment of infective endocarditis in adults: a concise guide. Clin Med 2004;4:545-50.
  2. Gould FK, Elliott TS, Foweraker J et al. Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2006;57:1035-42.
  3. National Institute for Health and Clinical Excellence. Prophylaxis against infective endocarditis: NICE guidance. London: NICE, 2008. Available from: http://www.nice.org.uk/Guidance/CG64
  4. Oakley C, Somerville W. Prevention of endocarditis. Br Heart J 1981;45:233-5.
  5. Dental Protection. Antibiotic cover for dental procedures - frequently asked questions. Available from: http://www.dentalprotection.org/assets/documents/ 2008_DPL_FAQ_Antibiotic_Prophylaxis_0308.pdf
  6. Ramsdale DR, Egred M, Palmer ND, Chalmers JAC. Antibiotic prophylaxis to prevent infective endocarditis should be given to patients. Heart 2007;eletter. Available from: http://heart.bmj.com/cgi/eletters/93/6/753-a#1477
  7. Bolam v Friern Hospital Management Committee 1957. Available from: http://oxcheps.new.ox.ac.uk/casebook/Resources/BOLAMV_1%20DOC.pdf