Clinical effects of theophylline on inspiratory muscle drive in tetraplegia

Theophylline has been shown to restore diaphragmatic function in animals following cervical spinal cord hemisection, which induces hemidiaphragm paralysis. Although theophylline had been used clinically in the treatment of various pulmonary diseases, its effects on respiratory muscle function in cervical spinal cord injured tetraplegics has not been studied. In the present case study, we evaluated a patient injured in 1979 with a chronic asymmetric C5-7 tetraplegia (left C5-6, right C6-7) before and alter receiving theophylline chronically by mouth for three weeks and again before and after receiving acute intravenous (IV) aminophylline after the effects of the chronic drug administration wore off. Neural activation to inspiratory muscles was assessed by right and left parasternal intercostal and diaphragm EMGs during quiet breathing and maximal inspiratory efforts. Global respiratory drive was assessed by P-100, and inspiratory muscle force was assessed by maximal inspiratory pressures and vital capacity. Both long-term orally administered and acute IV theophylline increased neural activation to the diaphragm, especially on the more affected left aide. Theophylline treatment was also associated with an increase in global central respiratory drive and inspiratory muscle force, without changing expiratory airflows. Left diaphragm EMG activity was markedly increased following the administration of theophylline. Of interest, upper parasternal intercostal EMG activity was also recruited on the left in spite of being below the level of cervical injury. We speculate that the administration of theophylline in selected patients with an asymmetric cervical spinal cord injury may activate latent bulbospinal respiratory pathways and improve inspiratory muscle function, reducing the likelihood of associated respiratory failure.