Palliative treatment of dyspnea with epidural methadone in advanced emphysema

Chest. 2005 Nov;128(5):3322-8. doi: 10.1378/chest.128.5.3322.


Study objectives: This study investigated whether epidural methadone perfusion at the thoracic level can mitigate dyspnea in patients with advanced emphysema.

Design: Open-label clinical trial without a control group.

Setting: University hospital.

Patients: The inclusion criteria were a diagnosis of emphysema, basal dyspnea index (Mahler scale) < or = 3, FEV(1) < or = 35%, and no indication for pneumoreduction or lung transplantation surgery.

Interventions: An epidural catheter was inserted at the thoracic level connected to a perfusion pump for administering methadone (6 mg/24 h). Assessments were made at baseline, 1 week, and 1 month after catheter insertion.

Measurements: Pulmonary function tests were performed, and determinations were made of arterial blood gas levels, respiratory control data, dyspnea quantification by Mahler transitional dyspnea index (TDI), and the Borg scale change with inspiratory resistive loading, 6-min walk (6MW) distance, and health-related quality of life using the Chronic Respiratory Disease Questionnaire.

Results: Of the nine patients studied, infection and catheter migration lead to suspension of treatment before the end of the study in two cases. A significant improvement in dyspnea occurred by 1 week: mean TDI, 3.77 (SD, 1.98) [p < 0.01]. After 1 month of treatment, there were significant improvements in the 6MW distance (mean, 35.33 m; SD, 17.03; p < 0.05), health-related quality of life (mean, 1.63; SD, 0.36; p < 0.05), and dyspnea (mean TDI, 5.33; SD, 2.16; p < 0.05). In addition, after 1 month, Paco(2) fell by 6.67 mm Hg (p < 0.05) and rapid shallow breathing index decreased from 38 to 27 (p < 0.05). These changes occurred without any alteration in the subject's ability to perceive or respond to inspiratory loading.

Conclusion: Epidural methadone perfusion at chest level can effectively palliate dyspnea and improve exercise capacity and quality of life in patients with advanced emphysema, without deterioration in respiratory control or lung function. These data suggest that modulation of spinal cord afferent signaling is an appropriate novel target for dyspnea control in chronic respiratory disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon Dioxide / blood
  • Dyspnea / drug therapy*
  • Dyspnea / etiology
  • Epidural Space
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Methadone / administration & dosage*
  • Oxygen / blood
  • Palliative Care
  • Pulmonary Emphysema / complications
  • Pulmonary Emphysema / drug therapy*
  • Quality of Life
  • Treatment Outcome


  • Carbon Dioxide
  • Oxygen
  • Methadone