Theophylline has a relatively low therapeutic index, ie, a narrow therapeutic-toxic serum concentration range, and since both its bronchodilatory efficacy and toxicity are related to its serum concentrations, it is important to recognize factors which might influence theophylline levels. Drug interaction has been reported between theophylline and erythromycin, cimetidine, phenobarbital, propranolol, isoproterenol, and terbutaline. Both isoproterenol and terbutaline2 have recently been shown to increase theophylline clearance in asthmatic children. Albuterol is another p-agonist extensively used in the management of acute asthma in conjunction with theophylline. We report a child who received continuous intravenous theophylline for the treatment of status asthmaticus and whose theophylline clearance was increased by intravenous administration of albuterol. buy antidepressants online
Theophylline blood concentrations were determined by the enzyme immunoassay method [Emit, Syva]. Theophylline clearance (T/cl) in L/kg/hr was calculated from the equation.
T/cl = R/C
where R is the infusion rate of theophylline (mg/kg/hr) and C is the concomitant theophylline concentration (μg/ml).
A 19-month-old boy was admitted to our ward with severe asthma. On admission, the child was afebrile weighing 12 kg (60th percentile), in mild respiratory distress, with a respiratory rate of 30 breaths per minute, substernal retractions, prolonged expiration, and diffuse expiratory wheezes. Physical examination was otherwise normal. His blood count, liver enzymes, blood urea nitrogen and creatinine values were all within normal limits, and his chest x-ray film revealed no infiltrates. He was treated with continous intravenous hydrocortisone (1 mg/kg/hr) and theophylline (0.9 mg/kg/hr) in conjunction with albuterol (2.5 mg in 2 ml) by nebulizer at four-hour intervals. Mild clinical improvement was observed after three days. However, during the next two days, the child’s condition deteriorated. Arterial blood gas values showed increasing hypoxia (Po2, 33 mm Hg) and hypercarbia (Pco2, 47 mm Hg). Theophylline infusion rate was increased to 1.2 mg/kg/hr, and the child was put in a humidity tent with oxygen. However, his condition did not improve, and intravenous isoproterenol was added. Theophylline levels prior to initiation of isoproterenol therapy ranged between 6.8 and 12 (xg/ml with a mean clearance of 0.10 (range 0.08 to 0.13) L/kg/hr. Theophylline clearance (T/cl) values are represented in Figure 1. Since the theophylline serum concentration during isoproterenol infusion was only 6.6 μg/ml, with a T/cl of 0.18 L/kg/hr, the theophylline infusion rate was increased to 1.5 mg/kg/hr. However, there was no clinical improvement in the child’s condition, and isoproterenol was substituted with intravenous albuterol given at a rate of 5 μg/kg/hr. During this period, further increments in the theophylline infusion rate up to 3 mg/kg/h were required, in order to achieve therapeutic theophylline levels. The T/cl remained high, reaching a peak of 0.24 L/kg/h. Due to technical reasons, albuterol infusion was withheld for 12 hours (Fig 1), during which time, T/cl declined markedly. Following the reinstitution of albuterol, T/cl again increased up to 0.21 L/kg/h. Since the child’s condition deteriorated with progressive hypoxia and hypercarbia, mechanical ventilation was instituted. During the next few hours, there was progressive improvement, allowing discontinuation of albuterol therapy The T/cl, measured a few hours later again, showed values of 0.13 and 0.10 L/kg/h, similar to those measured before the initiation of isoproterenol therapy
Figure 1. Theophylline clearance (L/kg/h) in a 19-month-old asthmatic boy during intravenous isoproterenol and albuterol therapy.