Gleadhill I C, Wise R A, Schonfeld S A, Scott P P, Guarnieri T, Levine J H, Griffith L S, Veltri E P
Johns Hopkins Hospital, Baltimore, Maryland.
Am J Med. 1989 Jan;86(1):4-10. doi: 10.1016/0002-9343(89)90221-0.
Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent.
Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days.
For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent.
An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity.
胺碘酮已被证实在许多心律失常、难治性室性心动过速和心室颤动病例中有效。肺部毒性是该药物可能的副作用,据报道每年发生率为2%至15%。为了确定胺碘酮对肺功能的影响,我们前瞻性地研究了91例接受该药物治疗的难治性心律失常患者的系列肺功能测试。
在0、3、6、12、18和24个月时测量肺活量和一氧化碳弥散量(DLCO),平均随访351天。
对于平均每日服用胺碘酮剂量为367毫克(范围:136至512毫克)的整个人群,肺活量指标或DLCO没有加速下降的情况。通过多变量分析对肺功能变化进行分析表明,老年患者DLCO值加速下降(p小于0.05),但在已有肺部疾病的患者或吸烟者中未出现这种情况。有4例患者(4.5%)出现了胺碘酮肺部毒性的临床证据,这与DLCO下降超过20%有关。所有4例患者在停药后均康复。另外15例患者没有肺部毒性的临床证据,但DLCO持续下降超过20%。这15例患者在接下来的11个月内未中断治疗,仍无症状。DLCO下降超过20%是临床上明显的胺碘酮肺部毒性的敏感检测指标,但阳性预测值仅为21%。
在没有毒性临床证据的情况下,单纯DLCO下降并不一定需要停用胺碘酮。DLCO值不变似乎是肺部毒性可靠的阴性预测指标。