Albuterol to Improve Respiratory Strength in SCI

Although the past 40 years has witnessed a substantial improvement in the acute and chronic management of persons with SCI, mortality remains high during the first year post-injury, and pulmonary complications including pneumonia, lung collapse (atelectasis), respiratory failure, and thromboembolism are the predominant cause. The propensity for pulmonary complications among subjects with SCI stems from paralysis of respiratory muscles. Injury to the cervical and upper thoracic cord significantly compromises function of the diaphragm, intercostal muscles, accessory respiratory muscles, and abdominal muscles. Respiratory muscle dysfunction is manifest as diminution in lung volumes, reduction in maximal static inspiratory and expiratory mouth pressures (MIP and MEP, respectively), and reduction in peak cough pressure and flow. Cough effectiveness is contingent upon both inspiratory and expiratory muscle strength; increasing the pressure-generating capacity of the inspiratory and expiratory muscles in persons with tetraplegia and high paraplegia may, therefore, translate to improved cough effectiveness and reduction in the propensity for atelectasis and, possibly, pneumonia. Respiratory muscle training, often utilizing simple hand-held portable resistive or threshold training devices, appears to have marginal effects on vital capacity and maximal static mouth inspiratory and expiratory pressures (MIP and MEP, respectively), although data is inconclusive. Pharmacologic interventions to improve respiratory muscle strength have received little attention in the SCI population. Studies involving oral beta-2 adrenergic agonists, which have been shown to elicit anabolic effects on skeletal muscle in young men and an increase in muscle strength among patients with facioscapulohumeral muscular dystrophy, have also demonstrated salutary effects in persons with SCI. There are many foreseeable advantages of a pharmacologic approach to improve respiratory muscle strength in persons with SCI. For instance, RMT can be physically demanding and time consuming, compliance can be an issue, and sustainable improvements have not been realized. The intent in the present proposal is to enroll a targeted cohort of 24 comparatively weaker subjects with tetraplegia and high paraplegia in a randomized, double-blind, placebo-controlled, parallel group trial to assess the effects of an oral beta-2 agonist upon respiratory muscle strength and cough effectiveness.