Clinical Experimentation: Lessons From Lung Volume Reduction Surgery

doi:10.1378/chest.110.1.230

Chest

Volume 110, Issue 1, July 1996, Pages 230-238

https://doi.org/10.1378/chest.110.1.230 Get rights and content

Although the advancement of medical science can occur only with the systematic evaluation of new interventions, novel therapies continue to be introduced and accepted prior to thorough study. The recent development of lung volume reduction surgery for emphysema provides an illustration of the unwillingness or the inability of the medical community, unconstrained by legal or reimbursement limitations, to assure the safety and efficacy of a new procedure prior to widespread utilization. Medical practitioners must learn to recognize the experimental nature of new procedures independent of the courts and third-party payers. The nature of the informed consent that must be obtained for an experimental therapy is different from that which is required for standard medical practice and this difference can provide a test of whether a new treatment is experimental. A comparison between the introduction of lung volume reduction surgery and the rigorous scrutiny required of any pharmacologic interventions for emphysema underscores the double standard that exists for evaluating new surgical (and some medical) innovations. Such a double standard cannot be defended on ethical or scientific grounds. Specific changes in the way experimental therapies are introduced and disseminated are suggested. Until all new medical and surgical interventions are required to undergo a thorough evaluation prior to becoming standard of care, the promise of evidence-based medicine can never be fulfilled. (CHEST 1996; 110:230-38)

Section snippets

HISTORY OF LUNG VOLUME REDUCTION SURGERY

The idea that patients with emphysema might derive benefit from reducing the volume of lung parenchyma was first tested by Brantigan and Mueller² in 1957. Despite the apparent improvement seen in several of their patients, the high perioperative mortality and substantial postoperative complication rate (particularly persistent air leaks) resulted in poor acceptance of the procedure. The development of a method that markedly decreases the incidence of air leaks after resection of emphysematous

ETHICS AND EXPERIMENTS

Much of the commentary regarding the ethical issues surrounding LVRS centers on whether the surgery is experimental. Some have argued that the operation simply represents an extension of an accepted practice of excising nonfunctional bullae from the lungs of patients with emphysema and that, as such, it is not experimental.⁷ We have disagreed, arguing that the uncertain risk/benefit ratio of the procedure together with the paucity of long-term follow-up requires that lung reduction, at that

INFORMED CONSENT

The difficulty in distinguishing between experimental and established treatment has led to calls to abandon such labels and for physicians to focus on providing meaningful justification for whatever they recommend for their patients.²³ While such a goal is laudable, we submit that there remains a fundamental difference between experimental and standard medical therapies that is manifested by the nature of the informed consent required for each and that cannot simply be dismissed. Although

ANALOGY WITH MEDICAL THERAPY

The recent decision by Medicare to stop reimbursing for LVRS and a request in the Federal Register (November 15, 1995) by the Agency for Health Care Policy and Research for information pertinent to an assessment of the safety and efficacy of the procedure indicate that, at least for these groups at that time, LVRS remained unproved, requiring further study to ascertain the likelihood, duration, and degree of benefit, as well as the risks, both short and long term. Challenges to this proposition

THE DOUBLE STANDARD

There is no FDA for the surgeon.²⁶ Recognizing this fact raises the obvious question of whether surgery is to be held to a different standard than the rest of the medicine. Despite disagreements about proper time frames and voluminous paperwork, the medical community fundamentally supports the work of the FDA and the requirements for evidence documenting the safety and efficacy of new medications prior to approval. The FDA requires extensive data, coming from carefully designed studies, which

SUGGESTIONS

The Belmont Report, the influential statement of the National Commission for the Protection of Human Subjects, recommends that “medical practice committees” be responsible for ensuring that major innovations undergo proper scientific evaluation.³⁵ We know of no such committees with the mandate or power to do so, but agree that both medical science and individual patients would be best served by requiring thorough evaluations of new procedures and interventions. Institutional review boards, the

CONCLUSION

Examining the history and current status of LVRS provides an opportunity to reassess the way new surgical therapies become standard therapy. This analysis also applies to some medical interventions that fall outside the purvey of federal regulatory agencies. The medical community must learn to recognize when treatments are experimental without relying on the determinations of courts and third-party payers. Although there may be no universal test to determine when a particular therapy has

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Cited by (26)

To treat or not to treat: On what should surgical therapy be based?
2015, Journal of Vascular Surgery
Dr C. Autious has just returned from the most prestigious vascular surgery meeting in America. At the meeting, one of the most prominent complex aneurysm surgeons arose to discuss a paper concerning a procedure he had developed and popularized over the last decade. Dr L. Uminous stunned the audience with his declaration that he no longer recommends that his namesake procedure be performed. Instead, he proclaimed that a new, radically different procedure be adopted immediately. He showed slides detailing the novel proposal but did not give data concerning results obtained. The recommended procedure is technically possible but seems to require a different skill set. Dr Autious has a patient scheduled for elective surgery that he had planned to use the Uminous procedure to treat. What should he do?
- A.
  Do the recommended procedure as best you can.
- B.
  Refer the patient to Dr Uminous.
- C.
  Offer the recommended procedure with full disclosure.
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  Give full disclosure and let the patient decide which procedure to use.
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  Put the procedure on hold until more information becomes available.
Innovative approaches to lung volume reduction for emphysema
2004, Chest
The 10 years of resurgent interest in lung volume reduction surgery (LVRS) and recent National Emphysema Treatment Trial findings for emphysema have stimulated a range of innovative alternative ideas aimed at improving outcomes and reducing complications associated with current LVRS techniques. Concepts being actively investigated at this time include surgical resection with compression/banding devices, endobronchial blockers, sealants, obstructing devices and valves, and bronchial bypass methods. These novel approaches are reaching the stage of clinical trials at this time. Theory, design issues, methods, potential advantages and limitations, and available results are presented. Extensive research in the near future will help to determine the potential clinical applicability of these new approaches to the treatment of emphysema symptoms.
Ethics of surgical innovation to treat rare diseases
2004, Journal of Vascular Surgery
Ethics of rapid surgical technological advancement
2000, Annals of Thoracic Surgery
Surgery for lung volume reduction
1999, Annales Francaises d'Anesthesie et de Reanimation
Définir la place de la chirurgie de réduction de volume pulmonaire (RVP) dans le cadre de l'emphysème non bulleux, discuter les mécanismes sous-jacents à l'amélioration fonctionnelle des patients opérés et proposer une stratégie de prise en charge médicale périopératoire.
Recherche dans la banque de données Medline^®, de tous les articles en langue anglaise, française et allemande (travaux originaux, commentaires, lettres, revues, éditoriaux), publiés depuis 1980 jusqu'en avril 1998. Les mots clés employés séparément ou en combinaison, étaient: lung volume reduction surgery, emphysema, respiratory failure, anaesthesia, lung transplantation. Les données de la littérature ont été analysées sous l'angle des mécanismes physiopathologiques et du rapport bénéfice/risque associés à la chirurgie de RVP.
Les principaux critères de sélection pour une RVP sont basés sur la sévérité de la dyspnée et de l'atteinte respiratoire obstructive (VEMS₁ ≤ 35% des valeurs prédites), le degré d'hyperinflation pulmonaire (VR ≥ 200%) et l'aspect hétérogène de l'emphysème. L'âge (> 75 ans), des antécédents de chirurgie thoracique, une atteinte prédominante des voies aériennes, une hypercapnie au repos (PaCO₂ > 52 mmHg), une HAP et des comorbidités graves représentent des critères d'exclusion. La résection pulmonaire (préfèrentiellement bilatérale) est pratiquée via stemotomie médiane, thoracotomie ou une vidéothoracoscopie assistée, par agrafage automatique le long d'une ligne de suture continue qui respecte la configuration originelle du poumon. Les territoires pulmonaires les plus détruits sont visualisés par la persistance des zones non collabées (espace mort), après l'exclusion unipulmonaire. L'anesthésie par des techniques IV ou inhalatoire est conduite avec le souci de réaliser un réveil et une extubation « sur table . La survenue peropératoire d'hyper-inflation dynamique ou d'un pneumothorax controlatéral doit être rapidement identifiée et corrigée.
En période postopératoire, l'analgésie est principalement basée sur l'administration par voie péridurale d'anesthésiques locaux et/ou des morphiniques et, par voie systémique d'adjuvants tels que les anti-inflammatoires non stéroïdiens et le propacétamol. En cas d'échec ou de contre-indication à une ponction péridurale, des agents morphiniques sont administrés uniquement par voie IV. La kinésithérapie respiratoire et la mobilisation précoces sont facilitées par une analgésie de qualité qui contribue ainsi à l'amélioration des échanges gazeux dans la période postopératoire immédiate.
La RVP induit chez 75 à 80% des patients, une amélioration significative des variables physiologiques (VEMS₁, VO₂max) et fonctionnelles (dyspnée, tolérance à l'effort, qualité de vie). La mortalité intrahospitalière moyenne est de l'ordre de 4%, alors que les complications les plus fréquentes sont représentées par les fuites aériques persistantes (20 %) et les infections bronchopulmonaires (5%).
Compte tenu des résultats favorables et d'un taux acceptable de complications périopératoires, la chirurgie de RVP peut être considérée comme une nouvelle alternative thérapeutique chez certains patients en insuffisance respiratoire. Des études ultérieures permettront d'affiner les critères de sélection, de préciser les techniques chirurgicale de choix et nous renseigneront sur le devenir « à long terme des opérés pour RVP.
To define the place of lung volume reduction surgery (LVRS) for non-bullous emphysema, to discuss the mechanisms of postoperative functional improvement and to suggest guidelines for perioperative medical management.
The Medline^® data base was searched for any article (original papers, editorials, comments, reviews) published in English, French or German, from 1980 to April 1998. The key words were: lung volume reduction surgery, emphysema, respiratory failure, anaesthesia, lung transplantation.
The data have been analysed to explain the physiological mechanisms underlying the postoperative improvements and to assess the risk-benefit ratio associated with LVRS. Finally, proposals are suggested for selection criteria and perioperative medical strategies.
Besides pharmacological treatment and lung transplantation, LVRS is considered as an alternative treatment for patients with end-stage pulmonary emphysema.
Perioperative management includes selective lung ventilation, continuous peridural analgesia and a general anaesthetic technique that can be easily reversed. Care should be taken to detect and rapidly correct dynamic hyperinflation, pneumothorax, tube malpositioning and major air leaks.
In a majority of selected patients (70–80%), resection of 20–30% of lung volume produces significant clinical and physiological improvement (dyspnoea, exercise capacity, FEV₁, VO₂max), as well as of the quality of life that has been attributed to greater elastic recoil, reduced respiratory workload and better diaphragmatic and right ventricular function. The most common complication is prolonged air leaks. In-hospital mortality varies widely (0–20%, with a median value at 4%), depending in part on the experience of the surgical team and on the selection criteria. Several factors may predict an unfavourable outcome: advanced age, hypercapnia, diffuse emphysema, predominant airway disease and previous thoracic surgery.
According to the favourable preliminary results and an acceptable incidence of perioperative complications, LVRS is presently considered as a new therapeutic option for some patients with respiratory failure. Future clinical studies should be focused on appropriate selection criteria, operative techniques and long term outcome data.
Lung volume reduction surgery for emphysema: Out on a limb without a NETT
1998, Mayo Clinic Proceedings
Lung volume reduction surgery (LVRS) has recently been rediscovered and offers the potential of improving the quality of life of patients with advanced emphysema. In this article, we discuss the historical and contemporary versions of LVRS. Although initial enthusiasm has been substantial, existing data seem insufficient to demonstrate the safety and efficacy of the procedure in comparison with conventional medical therapy. Fundamental questions remain regarding the long-term effects of an operation versus medical therapy, the optimal selection criteria, the best measures of efficacy, the mechanisms of improvement, the cost-effectiveness of the procedure, and the optimal surgical technique. Until such questions are answered, advising patients about the best management of their emphysema will be difficult. The National Emphysema Treatment Trial will address many of these issues and should be embraced by both health-care providers and patients.

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: revision accepted May 2.

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Chest

Special Reports: ReviewsClinical Experimentation: Lessons From Lung Volume Reduction Surgery

Section snippets

HISTORY OF LUNG VOLUME REDUCTION SURGERY

ETHICS AND EXPERIMENTS

INFORMED CONSENT

ANALOGY WITH MEDICAL THERAPY

THE DOUBLE STANDARD

SUGGESTIONS

CONCLUSION

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Chest

Soc Sci Med

J Thorac Cardiovasc Surg

Chest

Evidence-based medicine: A new approach to teaching the practice of medicine

JAMA

Surgical treatment of pulmonary emphysema

Am Rev Respir Dis

Technique to reduce air leaks after resection of emphysematous lung

Ann Thorac Surg

Reduction pneumoplasty for COPD [abstract]

Chest

Room to breathe

Saturday Evening Post

Breakthrough for emphysema patients

Saturday Evening Post

Is volume reduction surgery appropriate in the treatment of emphysema? yes

Am J Respir Crit Care Med

Special Reports: Reviews
Clinical Experimentation: Lessons From Lung Volume Reduction Surgery