MINOR SYMPTOMS ARE NOT PREDICTIVE OF ELEVATED THEOPHYLLINE LEVELS IN ADULTS ON CHRONIC THERAPY

Background: Theophylline toxicity is associated with significant morbi dity and mortality. While a relationship of the serum theophylline lev el to symptoms associated with toxicity has been described in acutely intoxicated or elderly patients, this relationship may not be valid in younger patients receiving chronic theophylline therapy. Objective: T his study was designed to define the predictive value and prevalence o f minor symptoms of theophylline toxicity in ambulatory asthmatic adul ts receiving chronic theophylline therapy with elevated serum theophyl line levels.Methods: We conducted a retrospective study to determine t he prevalence of symptoms in patients with elevated theophylline level s (>20 mg/L or 110 mu mol/L). A prospective study was performed to asc ertain the sensitivity, specificity, and predictive value of symptoms as an indication of elevated the theophylline level. In addition, we d escribe a patient who had a seizure in association with an elevated th eophylline level in the absence of any preceding symptom of theophylli ne toxicity. Results: We reviewed the result of 483 theophylline measu rements in 450 asthmatic patients. In 46 instances the theophylline le vel was >20 mg/L. Only three of these patients were symptomatic. Ninet y patients were prospectively studied with a total of Ill theophylline measurements of which 13 exceeded 20 mg/L. None of the symptoms tie, nausea or gastrointestinal upset; headache or palpitations, irregular heart beat, tremor, or shakiness) was a sensitive predictor of an elev ated theophylline level. Conclusions: Elevation of the theophylline le vel is frequently associated with lack of symptoms in young ambulatory asthmatic adults receiving chronic theophylline therapy. The question of whether cardiac or neurologic electrophysiologic abnormalities mig ht exist in the absence of symptoms is an issue that needs to be addre ssed. Clinicians should continue to monitor serum levels on a regular basis and prescribe this drug conservatively.