Comparison of the Effects of Nebulized Terbutaline with Intravenous Enprofylline in Patients with Acute Asthma: Materials and Methods

The following drugs were used in the study: sterile solution of enprofylline 10 mg/ml and a matching sterile placebo solution (saline); the terbutaiine was in the form of Bricanyl 1 percent nebulizer solution together with a matching placebo nebulizer solution. The enprofylline was administered in a dose of 0.2 ml or 2 mg/kg, made up to 100 ml with normal saline solution at room temperature, via a burette, over 20 minutes. One ml (10 mg) of terbutaiine solution was made up to 3 ml with normal saline solution for administration via a Hudson nebulizer and a face mask using a flow rate of 6 L/min of oxygen for ten minutes. Patients were stratified for age (less than 45 years, and 45 years or more) and treatment allocation was randomized into blocks of four using a computer program. A double-blind technique was used so that each patient received simultaneously both an intravenous infusion and a nebulized solution. The study was approved by the Clinical Investigation or Ethics Committees at each hospital.

After arrival at the hospital, a brief medical and a more detailed respiratory history were taken from each patient and consent was obtained. If the above inclusion and exclusion criteria were met, an intravenous line was inserted via an indwelling catheter in a forearm vein. Symptoms of possible unwanted effects which included headache, tremor, nausea and palpitations were recorded and graded on a scale from 0 = absent to 4 = very severe. Then FEVj (the best of up to three efforts on a volume displacement spirometer [Vitalograph]), systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured. Baseline venous blood samples taken for assay of xanthine levels and biochemical and hematologic status. Subsequently, an intravenous bolus infusion of enprofylline or placebo, and nebulization of terbutaline solution or placebo were commenced simultaneously with electrocardiographic monitoring. In the case of patients taking oral theophylline, the commencement of the study was to be deferred until a serum theophylline level was available, if this was practical within the hospital. Oxygen (28 percent) was given to each patient after nebulization was completed. The infusion was completed at 20 min and blood pressure, pulse rate, FEVi, blood sampling for enprofylline/theophylline and questioning for unwanted symptoms were repeated at this time and again at 40 and 60 min. At 60 min additional venous blood was taken for repeat measurements of biochemical and hematologic variables. On completion of the 60-minute study period, the patient was treated according to the clinicians assessment. itat on
The venous blood samples were collected in heparinized tubes and centrifuged at room temperature within 30 min and the plasma transferred to polyethylene tubes with screw caps and stored below – 18°C. All samples were analyzed for enprofylline in the Department of Clinical Pharmacology, Flinders Medical Centre, using a reverse phase liquid chromatographic method. Data analysis was by: analysis of variance of individual changes in FEVj, pulse rate, SBP, and DBP;* Wilcoxon two-sample test for increase above baseline for unwanted effects; and a paired t-test for biochemical and hematologic results at entry and at one h.