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Drug and Innovation Review

An Update on Lung Volume Reduction Surgery

E. Andrew Ochroch, MD
University of Pennsylvania
Philadelphia, PA

The National Emphysema Treatment Trial (NETT)1 was designed to determine if lung volume reduction surgery (LVRS) in combination with pulmonary rehabilitation led to greater improvements in functional capacity compared to pulmonary rehabilitation with medical therapy alone. The trial was a 4-year, multicenter study. Inclusion criteria were crafted to enroll patients with severe obstructive lung disease of varying anatomic distribution. Exclusion criteria eliminated patients at very high risk for perioperative morbidity, mortality, or other medical conditions that would decrease the likelihood of completing the trial. Once enrolled, all subjects went through 6 to 10 weeks of pulmonary rehabilitation prior to randomization. Subjects were then randomized to surgery or further medical management.

Surgical management consisted of bilateral stapled LVRS. The surgical approach was not consistent between centers. Eight centers performed LVRS by median sternotomy only, 3 centers performed LVRS by video assisted thoracoscopy (VATS) only, and 6 centers randomized patients to either median sternotomy or VATS. The goal of surgery was the removal of 25% to 30% of lung tissue from each side. Anesthetic management was standardized to include thoracic epidural analgesia. While epidural analgesia was originally planned only for patients undergoing median sternotomy, the use of epidural analgesia in VATS patients was center dependent.

An interim analysis2 of the first 1,033 subjects showed that there was excessive surgical mortality in the group of very high risk patients as defined by FEV1 < 20% predicted and either a homogenous distribution of emphysema or a DLCO < 20% predicted. LVRS in this group resulted in a 30-day mortality rate of 16% compared to a 30-day mortality rate of 0% in the medically treated group. While the survivors of surgery did exhibit modest improvements in FEV1 and distance walked in 6 minutes, their quality of life did not improve.

Analysis of the completed study of 1,218 randomized subjects3 showed that the risk of death was equal in the surgical and medical treatment groups. The surgically treated subjects had a greater improvement in exercise capacity compared to the medically treated patients. A greater than 10 watt increase in exercise capacity was observed in 15% of patients treated with LVRS compared to only 3% of patients treated medically. When the high-risk patients that were identified in the aforementioned interim analysis2 were excluded (140 patients), there was no difference in mortality between surgical and medical groups. Exercise capacity had improved by more than 10 watts in 16% of surgical patients as compared to 3% in medical patients.

Further subgroup analysis examining the effect of distribution of emphysema produced exciting results. Patients with poor exercise capacity and predominantly upper-lobe emphysema based on CT scan had a significant decrease in mortality as compared to their medically treated matches. The risk ratio for death was 0.47; p=0.005. Patients with non-upper-lobe predominant emphysema and high exercise exercise had increased surgical mortality with a risk ratio for death of 2.06; P=0.02.

Based on the subgroup analysis, the current trend is to prompt patients with upper-lobe emphysema and poor exercise tolerance to have LVRS. However, it is not clear from the publications how exercise capacity was measured and what cut-off was used to determine poor exercise capacity. Similarly, the exact criteria used to define upper-lobe predominance of emphysema based on the CT scan of the chest needs to be described in detail. Once these additional data become available the risks and benefits of LVRS in individual patients can be predicted with greater accuracy.

References

1. National Emphysema Treatment Trial Research Group. Rationale and design of The National Emphysema Treatment Trial: a prospective randomized trial of lung volume reduction surgery. The National Emphysema Treatment Trial Research Group. Chest. 116(6):1750-61, 1999

2. National Emphysema Treatment Trial Research Group. Patients at high risk of death after lung-volume-reduction surgery. New England Journal of Medicine. 345(15):1075-83, 2001

3. Fishman A. Martinez F. Naunheim K. Piantadosi S. Wise R. Ries A. Weinmann G. Wood DE. National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. New England Journal of Medicine. 348(21):2059-73, 2003


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