Scott A. Kolander, M.D.;([unkeyable...

Scott A. Kolander, M.D.;([unkeyable]) Charles C Nydegger M.D.;([unkeyable]) and R Stephen Porter, Pharm.D.([unkeyable])

Adverse cardiovascular efficiencys are commonly seen in bitter theophylline poisoning. Primary ST-T wave changes have not been described previously. We report T wave inversion associated with bitter theophylline toxicity in a 33-year-old woman with no evidence of organic heart disease. The T wave inversion resolv after treatment. Physicians should be alerted to possible T wave abnormalities in patients with chaste theophylline poisoning.

Theophylline is a widely used agent in the treatment of bronchospastic disorders. Toxicity generally flash on the minds at levels greater than 25 [unkeyable]g/ml.[1] stiff theophylline poisoning is characterized by way of cardiac arrhythmias, seizures, hypotension and cardiovascular collapse.[2-5] To our knowledge, primary T wave abnormalities have not been reported previously in connection with theophylline toxicity. We report T wave inversion associated with sharp theophylline toxicity.

CASE REPORT

A 33-year-old white woman with a history of asthma since childhood readyed to Hahnemann University Hospital forward February 1, 1988. The night prior to admission she exhibited progressive dyspnea and wheezing, and took a total of 2400 mg of theophylline through eight hours in an attempt to ameliorate her symptoms. The patient then became nauseous, tremulous, and experienced palpitations which brought her to the exigency room. She denied chest pain or dizziness. Her solitary medication was theophylline 300 mg twice daily. She smok the same pack of cigarettes daily. There is no history of intravenous mix with drugs use, but the patient admits to occasional cocaine use, which she claimed to have last taken couple weeks prior to admission.

upon presentation, she was afebrile with descendants pressure of 94/60 mm Hg The vibration rate was 80/min with a respiratory rate of 28/min. She appeared anxious, however was alert, oriented and in no respiratory distress. Physical examination was remarkable sole for a fine resting tremor and symmetric hyperreflexia.

The admission theophylline of the same height was 50.4 [unkeyable]g/ml. Serum potassium, calcium, phosphorus, and magnesium on a levels were normal. A stead air arterial blood gas determination revealed a pH of 750; [Pcosub2] 29 mm Hg; and [Posub2] 100 mm Hg Her chest x-ray film revealed single slight hyperinflation. The ER electrocardiogram revealed normal sinus number at 62/min with T wave inversion in leads 2 3 aVF, and [Vsub1] by the and of [V.sub.6] (see Fig 1). No dysrhythmia occurr during juncture room cardiac monitoring.

Eighteen hours after treatment with activated charcoal and magnesium citrate, her theophylline plain had decreased to 1.9 [unkeyable]g/ml. A repeat electrocardiogram at that time revealed almost unbroken resolution of the initial T wave inversion (Fig 1) Serial cardiac enzyme were negative for an acute myocardial infarction. Findings from a two-dimensional echocardiogram including Doppler was normal. Pulmonary function testing revealed normal spirometry, yet a decreased FEF 25-75% suggesting small airways disease.

A touchstone for urinary benzoylecognine (metabolite of cocaine) was negative. Follow-up ECG remained unchanged. Three days after admission, the patient was asked to hyperventilate, during which time simultaneous ABG analysis and ECG were performed. There were no significant ST-T wave changes at a pH of 748 and [Pcosub2] 32 mm Hg During treadmill exercise tolerance testing, the patient exercised into stage 3 of the Bruce protocol achieving and nothing else 69 percent of her predicted maximum heart rate. The exercise electrocardiogram showed normal physiologic ST-T wave changes without arrhythmia. Coronary arteriography revealed normal coronary arteries.

COMMENT

Studies of the electrophysiologic issues of theophylline have shown that it decreases the one and the other sinoatrial conduction time and His-Purkinje conduction interval.[6,7] These changes may be caused by the agency of direct action of theophylline or from associated increases in sympathetic tone,[8] however were not associated with T wave abnormalities.

Primary T wave inversion has been associated with myocardial ischemia, medicine effect, electrolyte imbalance, central nervous arrangement disease and hyperventilation.[9,10] Hyperventilation is unlikely to be the cause of T wave inversion in our patient since an electrocardiogram performed during hyperventilation showed no significant T wave changes. Central nervous arrangement disease can be associated with marked ECG waveform abnormalities, which are pondering to be due to altered autonomic tone or centrally induced structural cardiac changes.[11,12] Electrical stimulation of the animal brain has eventuateed in inversion and increased amplitude of the T wave.[13] It is possible that the central nervous order effects of toxic levels of theophylline are responsible for the T wave changes seen in our patient.

It is interesting that our patient did not have tachycardia while theophylline toxic. We postulate that our patient may have underlying sinus node dysfunction or perhaps had relative autonomic dysfunction secondary to chronic cocaine use. Chronic cocaine use has been associated with decreased tyrosine hydroxylase activity and decreased beta-adrenergic receptor binding sites.[14-16] It is possible that these issues of chronic cocaine use may have: 1) thwarted the increase in catecholamine release by the agency of theophylline, and 2) blunted the chronotropic force of the circulating catecholamines. Avakian and Manneh[17] have demonstrated in animals that chronic cocaine use will bluff the positive chronotropic and arrhythmogenic drifts induced by epinephrine.