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

Abstract

To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease post-operative from open heart surgery. Prospective open-label dose-escalation PK-PD study Tertiary pediatric cardiac intensive care unit 36 evaluable infants, ages 1 month – 24 months, post-operative from open heart surgery requiring mechanical ventilation Cohorts of 12 infants were enrolled sequentially to one of three intravenous loading dose – continuous infusion dexmedetomidine regimens: 0.35–0.25, 0.7–0.5, or 1–0.75 mcg/kg – 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/hour) and fewer analgesic medications (0.07 vs. 0.15 unit doses/hour) while receiving dexmedetomidine when compared to the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion with only 1 patient remaining intubated due to oversedation during the infusion. There was a decrease in heart rate while receiving dexmedetomidine compared to baseline, 132 vs. 161 beats/minute (bpm), but a higher heart rate when compared to post-infusion values, 132 vs. 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 post-operative hemodynamic changes that occur in infants post-operative from open heart surgery are multi-factorial. Although dexmedetomidine may play a role in decreasing heart rate immediately post-operative, the changes were not clinically significant and did not fall below post-infusion heart rates.