Puddu Paolo Emilio, Papalia Ugo, Schiariti Michele, Usta Coskun
Department of Cardiac Surgery, "La Sapienza" University, Rome, Italy.
Ital Heart J. 2004 Sep;5(9):693-701.
Dobutamina Studio Italiano Multicentrico (Do.S.I.M.) is a prospective, randomized, multicenter interuniversity Italian study aimed at assessing the effects of dobutamine on spontaneous variability of ventricular arrhythmias in sinus rhythm NYHA class III-IV patients with congestive heart failure (CHF).
Out of 74 pre-hoc estimated CHF patients, 68 (92%) were randomized electively to either being washed out of all active drugs except diuretics (group A) or to continue with the standard regimen including digitalis, diuretics and ACE-inhibitors (group B, standard therapy). In 63 patients, complete Holter data were obtained and are reported here. After 72 hours, in both groups, 48-hour Holter monitoring (Holter 1) was performed. The spontaneous variability of ventricular arrhythmias was assessed by calculating the natural logarithm of the sum of hourly incidences (during 48 consecutive hours) of index events such as the mean heart rate or the various forms of total and either sustained or non-sustained ventricular arrhythmias. The results were then grouped for the first and second 24-hour Holter periods. All patients were submitted to 10 microg/kg/min infusion of dobutamine for 72 hours and 48-hour Holter monitoring (Holter 2) was repeated 24 hours before the end of dobutamine infusion. The incidence of arrhythmia and the distribution of laboratory and echocardiographic variables was also studied in group A and B patients. The data of the two groups along with the intrapatient +/- 95% confidence intervals were pooled, both on and off dobutamine.
There was no significant difference between Holter 1 and Holter 2 in the rates of index events in 63 patients with regard to pro-arrhythmic effects. Pro-arrhythmic effects were seen during dobutamine infusion in 21% of cases, an effect which subsided (to 5%) when dobutamine was discontinued. Interestingly, the positive inotropic effects of dobutamine (based on ejection fraction changes) were parallel (22%) to the pro-arrhythmic changes, although they persisted long after dobutamine discontinuation (18%). The pro-arrhythmic effects of dobutamine, both during (5%) as well as after (1%) drug infusion, were unrelated to heart rate changes. The prevalence and incidence of non-sustained ventricular tachycardia due to dobutamine were 47 and 29% respectively.
In sinus rhythm patients with severe CHF, dobutamine had chronotropic effects and increased a depressed ejection fraction without significantly increasing arrhythmogenicity.
意大利多中心多巴酚丁胺研究（Do.S.I.M.）是一项前瞻性、随机、多中心的意大利大学间研究，旨在评估多巴酚丁胺对纽约心脏协会（NYHA）III-IV级充血性心力衰竭（CHF）窦性心律患者室性心律失常自发变异性的影响。
在74例预先估计的CHF患者中，68例（92%）被随机选择，要么停用除利尿剂外的所有活性药物（A组），要么继续使用包括洋地黄、利尿剂和血管紧张素转换酶抑制剂（ACE抑制剂）的标准治疗方案（B组，标准治疗）。在63例患者中获得了完整的动态心电图数据，并在此报告。72小时后，两组均进行了48小时动态心电图监测（动态心电图1）。通过计算指数事件（如平均心率或各种形式的持续性和非持续性室性心律失常）每小时发生率（连续48小时）之和的自然对数来评估室性心律失常的自发变异性。然后将结果按动态心电图监测的前24小时和后24小时分组。所有患者接受10μg/kg/min多巴酚丁胺静脉输注72小时，并在多巴酚丁胺输注结束前24小时重复进行48小时动态心电图监测（动态心电图2）。还研究了A组和B组患者心律失常的发生率以及实验室和超声心动图变量的分布情况。汇总了两组在使用和未使用多巴酚丁胺时的数据以及患者内±9%置信区间。
在63例患者中，就促心律失常作用而言，动态心电图1和动态心电图2之间的指数事件发生率无显著差异。21%的病例在多巴酚丁胺输注期间出现促心律失常作用，停用多巴酚丁胺后该作用减弱（至5%）。有趣的是，多巴酚丁胺的正性肌力作用（基于射血分数变化）与促心律失常变化平行（22%），尽管在多巴酚丁胺停用后仍持续存在（18%）。多巴酚丁胺在输注期间（5%）以及输注后（1%）的促心律失常作用与心率变化无关。多巴酚丁胺所致非持续性室性心动过速的患病率和发生率分别为47%和29%。
在重度CHF窦性心律患者中，多巴酚丁胺具有变时性作用，可提高降低的射血分数，而不会显著增加致心律失常性。
