Merry Alan F, Avery Edwin G, Nussmeier Nancy A, Playford Hugh R, Warman Guy R, Wang Yamei, Sladen Robert N
Faculty of Medical and Health Sciences, School of Medicine, The University of Auckland, Private Bag 92019, Auckland, 1003, New Zealand,
Can J Anaesth. 2014 May;61(5):398-406. doi: 10.1007/s12630-014-0131-z. Epub 2014 Apr 4.
We tested the hypothesis that clevidipine, a rapidly acting dihydropyridine calcium channel blocker, is not inferior to nitroglycerin (NTG) in controlling blood pressure before cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG).
In this double-blind study from October 4, 2003 to April 26, 2004, 100 patients undergoing CABG with CPB were randomized at four centres to receive intravenous infusions of clevidipine (0.2-8 μg·kg(-1)·min(-1)) or NTG (0.4 μg·kg(-1)·min(-1) to a clinician-determined maximum dose rate) from induction of anesthesia through 12 hr postoperatively. The study drug was titrated in the pre-CPB period with the aim of maintaining mean arterial pressure (MAP) within ± 5 mmHg of a clinician-predetermined target. The primary endpoint was the area under the curve (AUC) for the total time each patient's MAP was outside the target range from drug initiation to the start of CPB, normalized per hour (AUCMAP-D). The predefined non-inferiority criterion for the primary endpoint was a 95% confidence interval (CI) upper limit no greater than 1.50 for the geometric means ratio between clevidipine and NTG.
Total mean [standard deviation (SD)] dose pre-bypass was 4.5 (4.7) mg for clevidipine and 6.9 (5.4) mg for NTG (P < 0.05). The geometric mean AUCMAP-D for clevidipine was 283 mmHg·min·hr(-1) (n = 45) and for NTG was 292 mmHg·min·hr(-1) (n = 48); the geometric means ratio was 0.97 (95% CI 0.74 to 1.27). The geometric mean AUCMAP-D during aortic cannulation was 357.7 mmHg·min·hr(-1) for clevidipine compared with 190.5 mmHg·min·hr(-1) for NTG. Mean (SD) heart rate with clevidipine was 76.0 (13.8) beats·min(-1) compared with 81.5 (14.4) beats·min(-1) for NTG. There were no clinically important differences between groups in adverse events.
During CABG, clevidipine was not inferior to NTG for blood pressure control pre-bypass.
我们检验了如下假设，即在冠状动脉旁路移植术（CABG）期间，快速起效的二氢吡啶类钙通道阻滞剂克立硼罗在体外循环（CPB）前控制血压方面不劣于硝酸甘油（NTG）。
在这项于2003年10月4日至2004年4月26日开展的双盲研究中，100例接受CPB下CABG手术的患者在四个中心被随机分组，从麻醉诱导期至术后12小时接受静脉输注克立硼罗（0.2 - 8μg·kg⁻¹·min⁻¹）或NTG（0.4μg·kg⁻¹·min⁻¹至临床医生确定的最大剂量率）。在CPB前阶段滴定研究药物，目的是将平均动脉压（MAP）维持在临床医生预先确定目标的±5mmHg范围内。主要终点是从药物开始使用至CPB开始期间每位患者MAP超出目标范围的总时间的曲线下面积（AUC），按每小时进行标准化（AUCMAP - D）。主要终点的预定义非劣效性标准是克立硼罗与NTG几何均数比的95%置信区间（CI）上限不大于1.50。
旁路前克立硼罗的总平均[标准差（SD）]剂量为4.5（4.7）mg，NTG为6.9（5.4）mg（P < 0.05）。克立硼罗的几何平均AUCMAP - D为283mmHg·min·hr⁻¹（n = 45），NTG为292mmHg·min·hr⁻¹（n = 48）；几何均数比为0.97（95%CI 0.74至1.27）。在主动脉插管期间，克立硼罗的几何平均AUCMAP - D为357.7mmHg·min·hr⁻¹，而NTG为190.5mmHg·min·hr⁻¹。使用克立硼罗时的平均（SD）心率为76.0（13.8）次/分钟，而使用NTG时为81.5（14.4）次/分钟。两组在不良事件方面无临床重要差异。
在CABG期间，克立硼罗在旁路前控制血压方面不劣于NTG。
