Char Danton, Drover David R, Motonaga Kara S, Gupta Sanjiv, Miyake Christina Y, Dubin Anne M, Hammer Gregory B
Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA.
Paediatr Anaesth. 2013 Oct;23(10):898-905. doi: 10.1111/pan.12143. Epub 2013 Mar 18.
Dexmedetomidine is an alpha2-adrenergic agonist used for sedation and analgesia in children. We previously showed that dexmedetomidine depresses sinus and AV nodal function resulting in adverse hemodynamic effects such as bradycardia and increased blood pressure. We hypothesized that these effects of dexmedetomidine might be antagonized by co-administration of ketamine, which has sympathomimetic properties.
Twenty-two children (ages 5-17 years) undergoing electrophysiologic (EP) study and ablation for supraventricular tachycardia were enrolled. Patients were kept sedated with continuous infusion of propofol at a fixed rate. Hemodynamic and EP parameters were measured before and after a loading dose of dexmedetomidine (1 μg·kg(-1)). A continuous infusion of dexmedetomidine (0.7 μg·kg(-1) ·h(-1)) was initiated and a ketamine loading dose (1 mg·kg(-1)), followed by continuous infusion (1 mg·kg(-1) ·h(-1)), was given. A repeat set of hemodynamic and EP parameters were then measured at the time of projected peak tissue concentration for both drugs.
A significant increase in mean arterial pressure (MAP) was seen compared with baseline after loading of dexmedetomidine. This returned to baseline after co-administration of ketamine (mean difference between baseline and after ketamine 1.8 mmHg; 95%CI, -7.8 to 4.3; P = <0.001). A decrease in heart rate was seen after dexmedetomidine followed by a return to baseline after co-administration of ketamine (mean difference between baseline and after ketamine -6.5 bpm; 95%CI, -11.2 to -1.8; P = 0.005). Sinus node recovery time was lengthened after dexmedetomidine but returned to baseline after ketamine (mean difference between baseline and after ketamine -16.2 ms; 95%CI, -63 to 30; P = 0.014). QT was prolonged after dexmedetomidine and returned to baseline after ketamine (mean difference between baseline and after ketamine -34.2 ms; 95%CI, -48.4 to -20.2; P = 0.004). AV nodal effective refractory period was also impaired after dexmedetomidine and showed weak evidence for return to baseline function after ketamine (mean difference between baseline and after ketamine -22.8 ms; 95%CI, -40.2 to -5.2; P = 0.069).
The concurrent use of ketamine may mitigate the negative chronotropic effects of dexmedetomidine.
右美托咪定是一种α2肾上腺素能激动剂，用于儿童镇静和镇痛。我们之前表明，右美托咪定可抑制窦房结和房室结功能，导致心动过缓和血压升高等不良血流动力学效应。我们推测，右美托咪定的这些效应可能会被具有拟交感神经特性的氯胺酮联合使用所拮抗。
纳入22例年龄在5至17岁之间接受电生理（EP）研究和室上性心动过速消融术的儿童。患者以固定速率持续输注丙泊酚进行镇静。在给予负荷剂量的右美托咪定（1μg·kg-1）之前和之后测量血流动力学和EP参数。开始持续输注右美托咪定（0.7μg·kg-1·h-1），并给予氯胺酮负荷剂量（1mg·kg-1），随后持续输注（1mg·kg-1·h-1）。然后在两种药物预计的组织浓度峰值时重复测量一组血流动力学和EP参数。
给予右美托咪定负荷剂量后，平均动脉压（MAP）较基线显著升高。氯胺酮联合使用后恢复至基线水平（氯胺酮给药后与基线的平均差异为1.8mmHg；95%CI，-7.8至4.3；P = <0.001）。右美托咪定给药后心率下降，氯胺酮联合使用后恢复至基线水平（氯胺酮给药后与基线的平均差异为-6.5次/分钟；95%CI，-11.2至-1.8；P = 0.005）。右美托咪定给药后窦房结恢复时间延长，但氯胺酮给药后恢复至基线水平（氯胺酮给药后与基线的平均差异为-16.2毫秒；95%CI，-63至30；P = 0.014）。右美托咪定给药后QT间期延长，氯胺酮给药后恢复至基线水平（氯胺酮给药后与基线的平均差异为-34.2毫秒；95%CI，-48.4至-20.2；P = 0.004）。右美托咪定给药后房室结有效不应期也受损，氯胺酮给药后有微弱证据表明恢复至基线功能（氯胺酮给药后与基线的平均差异为-22.8毫秒；95%CI，-40.2至-5.2；P = 0.069）。
氯胺酮的同时使用可能减轻右美托咪定的负性变时作用。
