Scheinman M M, Levine J H, Cannom D S, Friehling T, Kopelman H A, Chilson D A, Platia E V, Wilber D J, Kowey P R
University of California, San Francisco, 94143-1354, USA.
Circulation. 1995 Dec 1;92(11):3264-72. doi: 10.1161/01.cir.92.11.3264.
Oral amiodarone effectively suppresses ventricular arrhythmias; however, full activity may take days or weeks. In patients with frequent, life-threatening ventricular arrhythmias, this delay is not acceptable. Thus, in these patients, the speed and dosing accuracy of an intravenous formulation would be beneficial. The goal of this study was to demonstrate the efficacy of intravenous amiodarone in patients with refractory, recurrent hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation by determining a dose response among three regimens.
A total of 342 patients were enrolled at 46 medical centers in the United States. Patients received one of three randomized, double-blind dose regimens delivering 125, 500, or 1000 mg during the first 24 hours. Supplemental infusions (150 mg) of intravenous amiodarone could be given to treat breakthrough ventricular arrhythmias. The key efficacy end points were the arrhythmia event rate, time to first arrhythmic event, and number of supplemental infusions administered. The event rate decreased with increasing doses: median values were 0.07, 0.04, and 0.02 events per hour for the 125-, 500-, and 1000-mg dose groups, respectively, representing a significant decrease from baseline event rates (P = .043), and approached significance in the overall test for trend (P = .067). There was a significant dose-related increase in the time to first event (trend test P = .025) and a significant dose-related decrease in the number of supplemental boluses per hour (trend test P = .043). Hypotension was the most common (26%) treatment-emergent adverse event during intravenous amiodarone therapy; there was no dose-response relationship. Seventy-eight percent of the patients survived to at least 48 hours.
Intravenous amiodarone is effective for the treatment of recurrent, life-threatening ventricular tachyarrhythmias.
口服胺碘酮能有效抑制室性心律失常；然而，其完全起效可能需要数天或数周。对于频发、危及生命的室性心律失常患者，这种延迟是不可接受的。因此，对于这些患者，静脉制剂的给药速度和剂量准确性将是有益的。本研究的目的是通过确定三种给药方案之间的剂量反应，来证明静脉注射胺碘酮对难治性、复发性血流动力学不稳定的室性心动过速或室颤患者的疗效。
美国46个医学中心共纳入342例患者。患者在最初24小时内接受三种随机、双盲剂量方案之一，分别给予125、500或1000mg。可给予静脉胺碘酮补充输注（150mg）以治疗突破性室性心律失常。关键疗效终点为心律失常事件发生率、首次心律失常事件发生时间以及补充输注的次数。事件发生率随剂量增加而降低：125mg、500mg和1000mg剂量组每小时的中位数分别为0.07次、0.04次和0.02次事件，较基线事件发生率显著降低（P = 0.043），在总体趋势检验中接近显著性（P = 0.067）。首次事件发生时间有显著的剂量相关增加（趋势检验P = 0.025），每小时补充推注次数有显著的剂量相关减少（趋势检验P = 0.043）。低血压是静脉胺碘酮治疗期间最常见的（26%）治疗中出现的不良事件；不存在剂量反应关系。78%的患者存活至少48小时。
静脉注射胺碘酮对复发性、危及生命 的室性快速心律失常有效。
