Effects of theophylline on pulmonary function in patients with traumatic tetraplegia

Abstract

Background/objectives: To assess the effects of theophylline on pulmonary function in patients with chronic traumatic tetraplegia, we conducted a double-blind placebo-controlled crossover study in 10 patients.

Methods: The patients (age: 41 +/- 3 years; time from injury: 16 +/- 3 years; neurological levels: C3 to C7-T1) were randomized to receive oral theophylline or placebo for 6 weeks. After 2 months of washout, the patients received the medication not taken in the first trial for an additional 6 weeks. We measured lung volumes, expiratory flow rates, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) at both baseline and at the end of each treatment arm. Theophylline blood serum assays were measured during the first week of the treatment and on the day of respiratory measurements.

Results: Mean theophylline level on the day of treatment completion was 12.6 +/- 1.4 microg/mL. In analyzing the data from the group of 10 patients, the percent changes from baseline in total lung capacity, forced vital capacity, forced expiratory volume at 1 second, MIP, and MEP did not differ significantly between the two treatment arms (P > 0.05 in all).

Conclusion: These data show that in this small group of 10 subjects with chronic tetraplegia, administration of oral theophylline did not improve pulmonary function.

Figures

Figure 1. Inspiratory drive to phrenic motoneurons is mediated by medullary neurons in the rostral division of the ventral respiratory group (rVRG). These neurons project bilaterally to the phrenic nuclei. Both the crossed and uncrossed rVRG pathways have latent spinal decussating collaterals that also innervate the phrenic nuclei (ie, the crossed phrenic pathways). Hemisection rostral to the phrenic nucleus interrupts (dotted lines) the major bulbospinal drive to the ipsilateral phrenic nucleus, which results in paralysis of the left hemidiaphragm. Systemic administration of theophylline enhances descending inspiratory drive and activates the previously latent crossed phrenic pathways, which can now depolarize phrenic motoneurons ipsilateral and caudal to the hemisection. Arrows indicate the pathway followed by respiratory impulses to restore function to the hemi-diaphragm paralyzed by the spinal cord injury. (Reprinted from reference 29 with permission from Academic Press.)

Figure 2. Percent changes from baseline measurements in percent predicted (% pred) values for total lung capacity (TLC), forced vital capacity (FVC), and forced expiratory volume at 1 second (FEV1) during theophylline (Th) (cross-hatched bars) or placebo (Pl) (solid bars) treatment. No statistically significant changes were found within the group of 10 patients with tetraplegia (P > 0.05).

Figure 3. Percent changes from baseline measurements in maximal inspiratory (MIP) and maximal expiratory pressure (MEP) in the group of 10 patients after taking theophylline (Th) or placebo (Pl). There is a trend for an increase in both pressures, which did not reach statistical significance.