A Dose-Response Study of Dexmedetomidine Administered as the Primary Sedative in Infants Following Open Heart Surgery

作者：Su Felice^*; Nicolson Susan C; Zuppa Athena F

来源：Pediatric Critical Care Medicine, 2013, 14(5): 499-507.

DOI：10.1097/PCC.0b013e31828a8800

• congenital heart disease
• dexmedetomidine
• infant
• pharmacodynamics
• sedation

Objective:
To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery.
Design:
Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study.
Setting:
Tertiary pediatric cardiac ICU.
Patients:
Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation.
Interventions:
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.
Measurements and Main Results:
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.
Conclusions:
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.

• 出版日期2013-6