七氟烷、丙泊酚和瑞芬太尼对气腹及腹腔镜手术血流动力学反应的影响：一项随机对照试验

文献信息

中文摘要

背景： 尽管已就七氟烷、丙泊酚和阿片类药物对喉镜检查运动反应的相互作用进行了研究，但其在手术刺激期间的血流动力学影响仍未得到探索。因此，我们评估了七氟烷、丙泊酚和瑞芬太尼对气腹及腹腔镜手术血流动力学反应的影响。
方法： 计划接受择期腹腔镜手术的美国麻醉医师学会（ASA）身体状况I或II级患者被随机分配到六组之一，分别接受七氟烷-瑞芬太尼、丙泊酚-瑞芬太尼或七氟烷-丙泊酚-瑞芬太尼的不同组合。采用上下法测定七氟烷和丙泊酚与瑞芬太尼联用时的Ce50 BARPP（气腹），并用线性相加模型描述三种药物对平均动脉压（MAP）反应的相互作用。手术期间，在固定浓度的七氟烷（1 vol%）、丙泊酚（3 µg mL-1）或七氟烷（0.5 vol%）加丙泊酚（1.5 µg mL-1）下，滴定瑞芬太尼以维持MAP <100 mm Hg。手术期间瑞芬太尼与MAP之间的关系用线性混合效应模型描述。
结果： 分析了155例患者的数据。在瑞芬太尼5 ng mL-1时，七氟烷的Ce50 BARPP（95% CI）为1.56（1.18-1.95）vol%，丙泊酚为4.82（4.29-5.36）µg mL-1。在瑞芬太尼3 ng/ml加丙泊酚1.8 µg mL-1或七氟烷0.6 vol%时，该值分别为2.2（2.0-2.4）vol%和5.9（5.7-6.0）µg mL-1。药物相互作用模型显示丙泊酚缩放因子（scaleSP）为0.31（0.19-0.44），代表丙泊酚相对于七氟烷的效价，瑞芬太尼常数kremi为2.03（0.82-3.24），代表瑞芬太尼的催眠节省效应。手术期间瑞芬太尼的中位数（四分位距）在SR、PR和SPR组分别为6.4（5.8-7.7）、4.9（3.6-6.7）和5.0（3.7-6.0）ng mL-1。MAP与瑞芬太尼浓度不相关，证明存在药物滴定悖论。
结论： 七氟烷相对于丙泊酚在降低气腹MAP反应方面的相对效价与喉镜检查耐受性相似，但与催眠终点不同。瑞芬太尼降低MAP反应的效果在与七氟烷或丙泊酚联用时相似。由于滴定至动态临床终点会解耦药物输入与临床结果之间的传统关系，滴定数据不能用于验证药效动力学模型。

英文摘要

BACKGROUND: Although the interaction of sevoflurane, propofol, and opioids has been investigated regarding motor response to laryngoscopy, their hemodynamic impact during surgical stimulation remains unexplored. We therefore assessed the effect of sevoflurane, propofol, and remifentanil on the hemodynamic response to pneumoperitoneum and laparoscopic surgery.
METHODS: The American Society of Anesthesiologists (ASA) physical status I or II patients scheduled for elective laparoscopic surgery were randomly assigned to one of six groups with different combinations of sevoflurane-remifentanil, propofol-remifentanil, or sevoflurane-propofol-remifentanil, respectively. The Ce50 BARPP (pneumoperitoneum) for sevoflurane and propofol in combination with remifentanil was determined with the up-and-down method, and the interaction of the three drugs on mean arterial pressure (MAP) response was described with a linear-additive model. During surgery remifentanil was titrated to keep the MAP <100 mm Hg at fixed concentrations of sevoflurane (1 vol%), propofol (3 µg mL-1), or sevoflurane (0.5 vol%) plus propofol (1.5 µg mL-1). The relationship between remifentanil and MAP during surgery was described with a linear mixed-effects model.
RESULTS: Data of 155 patients were analyzed. At remifentanil 5 ng mL-1 the Ce50 BARPP (95% CI) of sevoflurane was 1.56 (1.18-1.95) vol%, and of propofol 4.82 (4.29-5.36) µg mL-1. At remifentanil 3 ng/ml plus either propofol 1.8 µg mL-1 or sevoflurane 0.6 vol%, the values were 2.2 (2.0-2.4) vol% and 5.9 (5.7-6.0) µg mL-1. The drug interaction model revealed a propofol scaling factor (scaleSP) of 0.31 (0.19-0.44), representing the potency of propofol relative to sevoflurane, and a remifentanil constant kremi of 2.03 (0.82-3.24), representing the hypnotic-sparing effect of remifentanil. The median (interquartile range) of remifentanil during surgery was 6.4 (5.8-7.7), 4.9 (3.6-6.7), and 5.0 (3.7-6.0) ng mL-1 in groups SR, PR, and SPR, respectively. The MAP did not correlate with the remifentanil concentrations, demonstrating evidence for the drug titration paradox.
CONCLUSIONS: The relative potency of sevoflurane to propofol in reducing the MAP response to pneumoperitoneum is similar to that for tolerance of laryngoscopy but differs from that for hypnotic endpoints. The effect of remifentanil on reducing the MAP response is similar whether it is combined with sevoflurane or propofol. Because titration to a dynamic clinical end point decouples the traditional relationship between drug input and clinical outcome, titration data cannot be used to validate pharmacodynamic models.