Shannon M, Lovejoy F H
Program in Clinical Pharmacology/Toxicology, Children's Hospital, Boston, MA 02115.
Arch Intern Med. 1990 Oct;150(10):2045-8.
To identify risk factors for the development of seizures and cardiac arrhythmias after chronic, unintentional theophylline intoxication we monitored the clinical course of 72 consecutive patients referred to a regional poison center with chronic theophylline intoxication (serum theophylline concentration, greater than or equal to 167 mumol/L after protracted use). The median age of the sample was 47.5 years (range, 4 days to 91 years). Median peak theophylline concentration was 239 mumol/L, with a range of 167 to 722 mumol/L. A life-threatening event (LTE) occurred in 28 patients (39%) that included seizures in eight and a major cardiac arrhythmia in 22. The median peak (theophylline) of patients who had an LTE vs those who did not was 235.8 vs 238.7 mumol/L. However, the median age of patients with an LTE compared with those without an LTE was significantly greater (70.5 vs 18.0 years). Stratification of data by chronologic age revealed a stepwise increase in the frequency of LTE with advancing years: patients more than 75 years old had a 16.7-fold greater risk of LTE than patients less than 25 years old (95% confidence interval, 3.56, 77.5) despite comparable intergroup median serum (theophylline). These data suggest the primary determinant of LTEs after chronic theophylline intoxication is chronologic age. Elderly patients have an inordinately greater risk of LTE than younger patients. Peak serum theophylline concentration cannot predict which patients with chronic theophylline intoxication will have an LTE. Finally, these data indicate that theophylline should be used cautiously and with frequent monitoring of serum theophylline concentrations in elderly patients.
为了确定慢性非故意性氨茶碱中毒后癫痫发作和心律失常发生的危险因素，我们对72例连续转诊至某地区毒物中心的慢性氨茶碱中毒患者（长期使用后血清氨茶碱浓度大于或等于167μmol/L）的临床病程进行了监测。样本的中位年龄为47.5岁（范围为4天至91岁）。氨茶碱峰值浓度中位数为239μmol/L，范围为167至722μmol/L。28例患者（39%）发生了危及生命的事件（LTE），其中8例出现癫痫发作，22例出现严重心律失常。发生LTE的患者与未发生LTE的患者的氨茶碱峰值中位数分别为235.8μmol/L和238.7μmol/L。然而，发生LTE的患者与未发生LTE的患者相比，中位年龄显著更大（70.5岁对18.0岁）。按年龄分层的数据显示，随着年龄增长，LTE的发生频率呈逐步上升趋势：尽管组间血清（氨茶碱）中位数相当，但75岁以上的患者发生LTE的风险比25岁以下的患者高16.7倍（95%置信区间为3.56至77.5）。这些数据表明，慢性氨茶碱中毒后LTE的主要决定因素是年龄。老年患者发生LTE的风险比年轻患者高得多。血清氨茶碱峰值浓度无法预测哪些慢性氨茶碱中毒患者会发生LTE。最后，这些数据表明，在老年患者中应谨慎使用氨茶碱，并频繁监测血清氨茶碱浓度。
