Department of Pediatrics, Stanford University, Palo Alto, CA, USA.
Pediatr Crit Care Med. 2013 Jun;14(5):499-507. doi: 10.1097/PCC.0b013e31828a8800.
To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery.
Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study.
Tertiary pediatric cardiac ICU.
Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation.
Cohorts of 12 infants were enrolled sequentially to one of the three IV loading doses of dexmedetomidine (0.35, 0.7, and 1 mcg/kg) over 10 minutes followed by respective continuous infusions (0.25, 0.5, and 0.75 mcg/kg/hr) for up to 24 hours.
Dexmedetomidine plasma concentrations were obtained at timed intervals during and following discontinuation of infusion. Pharmacodynamic variables evaluated included sedation scores, supplemental sedation and analgesia medication administration, time to tracheal extubation, respiratory function, and hemodynamic parameters. Infants achieved a deeper sedation measured by the University of Michigan Sedation Scale score (2.6 vs 1) despite requiring minimal supplemental sedation (0 unit doses/hr) and fewer analgesic medications (0.07 vs 0.15 unit doses/hr) while receiving dexmedetomidine compared with the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion. Only one patient remained intubated due to oversedation during the infusion. While receiving dexmedetomidine, there was a decrease in heart rate compared with baseline, 132 versus 161 bpm, but there was an increase in heart rate compared with postinfusion values, 132 versus 128 bpm. There was no statistically or clinically significant change in mean arterial blood pressure.
Dexmedetomidine administration in infants following open heart surgery can provide improved sedation with reduction in supplemental medication requirements, leading to successful extubation while receiving a continuous infusion. The postoperative hemodynamic changes that occur in infants postoperative from open heart surgery are multifactorial. Although dexmedetomidine may play a role in decreasing heart rate immediately postoperative, the changes were not clinically significant and did not fall below postinfusion heart rates.
评估右美托咪定在先天性心脏病心脏直视手术后婴儿中的剂量反应关系。
前瞻性开放标记剂量递增药代动力学-药效学研究。
三级儿科心脏 ICU。
36 名可评估的婴儿，年龄 1-24 个月，心脏直视手术后需要机械通气。
连续纳入 12 名婴儿，分别接受三种右美托咪定静脉负荷剂量（0.35、0.7 和 1 mcg/kg）中的一种，持续 10 分钟，然后分别给予持续输注（0.25、0.5 和 0.75 mcg/kg/hr），最长 24 小时。
在输注过程中和输注停止后，以时间间隔获得右美托咪定的血浆浓度。评估的药效学变量包括镇静评分、补充镇静和镇痛药物的管理、气管拔管时间、呼吸功能和血流动力学参数。与 12 小时随访期间相比，婴儿在接受右美托咪定时达到更深的镇静状态，这是通过密歇根大学镇静评分（2.6 分对 1 分）测量的，尽管需要最小剂量的补充镇静（0 单位剂量/小时）和更少的镇痛药物（0.07 单位剂量/小时对 0.15 单位剂量/小时）。与接受右美托咪定时相比，31 名患者在接受右美托咪定输注时成功拔管。只有一名患者在输注过程中因过度镇静而继续插管。在接受右美托咪定时，与基础值相比，心率下降，132 次/分对 161 次/分，但与输注后值相比，心率增加，132 次/分对 128 次/分。平均动脉血压无统计学或临床意义的变化。
在心脏直视手术后的婴儿中给予右美托咪定可提供更好的镇静作用，减少补充药物的需求，从而在接受连续输注时成功拔管。接受心脏直视手术后婴儿发生的术后血流动力学变化是多因素的。虽然右美托咪定可能在术后立即发挥降低心率的作用，但变化无临床意义，且未低于输注后心率。
