The effect of theophylline on the mucociliary clearance function in ventilated intensive care patients

Abstract

Mucociliary clearance represents an important protective mechanism of the upper and lower respiratory tracts whereby inhaled particles and micro-organisms are removed from the tracheobronchial system. In incubated intensive care unit (ICU) patients, impaired ciliary function and mucus transport are associated with pulmonary complications [9]. Some authors have shown that theophylline increases mucus transport in healthy subjects and patients with chronic bronchitis [8, 16, 31, 36]. However, other investigators have found unconvincing or conflicting results [4, 20, 25]. Therefore, we studied the influence of theophylline on bronchial mucus transport velocity (BTV) in ventilated ICU patients. METHODS. The study was approved by the ethnics committee of our hospital. In a placebo-controlled double-blind study, the effect of therapeutic serum concentrations (10-20 micrograms/ml) of theophylline on BTV in ventilated patients in a surgical ICU was investigated. Group 1 (n = 10) served as controls and received placebo. The patients of group 2 (n = 10) were given intravenous infusions of 5 mg/kg body weight theophylline over 20 min, followed by 1 mg/kg per hour. Before administration of theophylline and 1 h after starting the infusion BTV, serum theophylline concentrations, and arterial blood gases were measured. Heart rate and blood pressure were registered every 5 min. In an additional study, the effect of theophylline on BTV at subtherapeutic serum concentrations (5 micrograms/ml) was investigated. BTV was measured with a small volume (0.05-0.08 ml) of albumin microspheres labeled with technetium-99m, which was deposited on the dorsal surface at the lower ends of the right and left main bronchi via a catheter placed in the inner channel of a fibre-optic bronchoscope. The movement of the microspheres towards the trachea was visualised and recorded using a scintillation camera [10]. RESULTS. The theophylline treatment induced a significant improvement in BTV from 3.8 to 7.6 mm/min in the left main bronchus and from 0.5 to 5.4 mm/min in the right, while placebo was inactive. The increase in BTV, however, was associated with an increase in heart rate; in 3 patients the theophylline infusion had to be stopped because of severe tachycardia. Blood gases and blood pressures did not change. Theophylline at subtherapeutic concentrations had no effect on either BTV or heart rate. CONCLUSIONS. Theophylline at therapeutic concentrations improves bronchial mucus transport in intubated ICU patients. The increase in BTV may be associated with severe tachycardia, and therefore routine application cannot be recommended.